Affinage

ISL1

Insulin gene enhancer protein ISL-1 · UniProt P61371

Length
349 aa
Mass
39.0 kDa
Annotated
2026-04-28
100 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ISL1 is a LIM-homeodomain transcription factor that serves as a master regulator of cell fate specification across an extraordinary range of tissues, including cardiac progenitors, pancreatic islet cells, motor and sensory neurons, retinal ganglion cells, striatal projection neurons, and auditory spiral ganglion neurons. Its two N-terminal LIM domains exert cis-inhibitory control over DNA binding by the homeodomain, and relief of this autoinhibition—together with assembly into cell-type-specific hexameric complexes with LHX3 (motor neurons) or LHX8 (forebrain cholinergic neurons) and the obligate coregulators Ldb1 and SSBP3—enables ISL1 to function as a pioneer transcription factor that opens compacted chromatin in concert with the Brg1–Baf60c SWI/SNF remodeling complex to establish epigenetic commitment to lineage-specific gene programs (PMID:7901000, PMID:24763339, PMID:31024170, PMID:23193182, PMID:26495868). ISL1 directly binds and activates batteries of target genes governing cardiomyocyte fate and pacemaker identity (Tbx3, calcium channel subunits, Ank2, Fgf10, MEF2C), pancreatic endocrine maturation (MafA, Pdx1, Glut2, Arx, insulin), cholinergic neurotransmitter pathway genes, and retinal ganglion cell specification (together with Pou4f2), while simultaneously repressing alternative lineage programs (PMID:26193633, PMID:25028525, PMID:21388963, PMID:25775587, PMID:24351932). Loss-of-function mutations in ISL1 are linked to congenital heart defects in humans, including double outlet right ventricle, and deletion of the ISL1 chromosomal region is associated with tracheo-esophageal malformations (PMID:30390123, PMID:31484864, PMID:31813798).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1993 High

    Established that ISL1's LIM domains are not mere structural appendages but act as intramolecular repressors of homeodomain DNA binding, revealing a built-in autoinhibitory switch that must be relieved for transcriptional activation.

    Evidence In vitro DNA-binding assays with truncation mutants and in vivo reporter assays in cultured cells

    PMID:7901000

    Open questions at the time
    • Identity of the physiological signal or cofactor that relieves LIM-domain autoinhibition in vivo was unknown
    • Structural basis of intramolecular inhibition not resolved
  2. 1997 High

    Demonstrated that ISL1 is indispensable for the genesis of all pancreatic endocrine islet cell types and for dorsal mesenchymal development, establishing ISL1 as a master regulator of endocrine pancreas formation.

    Evidence ISL1-null mouse embryos analyzed by histology; mesenchyme rescue experiments in vitro

    PMID:9000074

    Open questions at the time
    • Direct transcriptional targets in endocrine precursors were unidentified
    • Whether ISL1 acts in mature beta-cell function beyond development was unknown
  3. 2000 High

    Revealed that ISL1 physically interacts with the estrogen receptor and modulates its dimerization and DNA-binding activity, expanding ISL1's functional repertoire beyond classical homeodomain target gene activation to nuclear receptor crosstalk.

    Evidence Co-IP, GST pulldown, EMSA, and reporter assays

    PMID:11043578

    Open questions at the time
    • Physiological significance of ISL1–ER interaction in specific tissues not established
    • Whether the interaction occurs in endogenous chromatin context was untested
  4. 2003 Medium

    Identified an alternatively spliced ISL1 isoform (ISL1-beta) with enhanced transactivation potency on the insulin promoter and showed ISL1-alpha undergoes phosphorylation, introducing post-translational regulation as a mechanism controlling ISL1 activity.

    Evidence cDNA cloning, reporter assays, immunofluorescence, phosphorylation analysis

    PMID:14664703

    Open questions at the time
    • Identity of the kinase phosphorylating ISL1-alpha was unknown
    • Functional consequence of phosphorylation on DNA binding or cofactor recruitment was not determined
  5. 2006 High

    Showed ISL1 synergizes with HNF4α through direct physical interaction (via homeodomain and LIM1 domain) to activate metabolic gene promoters in pancreatic cells, establishing ISL1 as a combinatorial transcriptional partner for hepatocyte nuclear factors.

    Evidence Co-IP, GST pulldown, domain mapping with deletion mutants, ChIP, luciferase reporter assays

    PMID:17022998

    Open questions at the time
    • Genome-wide scope of ISL1–HNF4α co-regulation was uncharacterized
    • Whether this interaction is conserved outside rodent beta-cells was untested
  6. 2007 High

    Placed ISL1 downstream of Wnt/β-catenin signaling in cardiovascular progenitors: β-catenin directly binds the ISL1 promoter and is required for ISL1 expression, while Wnt signaling promotes ISL1+ progenitor expansion through an FGF signaling axis, defining the core upstream signaling module controlling ISL1 in heart development.

    Evidence ChIP for β-catenin on ISL1 promoter; conditional β-catenin gain- and loss-of-function in ISL1-Cre mice; Wnt3a feeder co-culture; gene expression profiling of FGF ligands

    PMID:17519333 PMID:17607356 PMID:18371348

    Open questions at the time
    • Precise chromatin mechanism by which β-catenin activates ISL1 transcription was unresolved
    • Whether Notch and Wnt signals converge on the same ISL1 enhancer elements was unknown
  7. 2008 High

    Conditional knockouts across neuronal and cardiac lineages established ISL1 as essential for retinal ganglion cell survival, sensory neuron subtype specification (nociceptor identity via TrkA/Runx1), and cardiac progenitor differentiation into cardiomyocytes and smooth muscle, revealing a recurring role as a cell-type fate switch.

    Evidence Retina-specific, sensory neuron-specific, and cardiac progenitor-specific conditional ISL1 KOs; microarray; apoptosis and cell cycle analysis

    PMID:18460603 PMID:18849985 PMID:19620969

    Open questions at the time
    • Direct transcriptional targets mediating RGC survival were not identified
    • Whether ISL1 acts continuously or transiently in sensory neuron maintenance was unresolved
  8. 2009 High

    Identified MafA as a direct ISL1 target in pancreatic islets and showed ISL1 synergizes with BETA2 via LIM-domain–bHLH interaction to activate insulin gene transcription, defining the combinatorial code for beta-cell-specific gene expression.

    Evidence Conditional ISL1 deletion at E13.5; ChIP on islet cells; Co-IP and EMSA with domain mutants; reporter assays

    PMID:19502415 PMID:19619559

    Open questions at the time
    • Genome-wide catalog of ISL1 targets in mature islet cells was lacking
    • Whether ISL1–BETA2 complex formation is regulated remained unknown
  9. 2011 High

    Extended ISL1's role beyond endocrine specification to direct transcriptional regulation of cell proliferation genes (c-Myc, CyclinD1) in islet cells, and to limb patterning where ISL1 regulates the Hand2–Shh pathway for hindlimb field establishment and promotes β-catenin nuclear accumulation.

    Evidence ChIP and reporter assays for c-Myc/CyclinD1; conditional ISL1 KO in hindlimb mesoderm; nuclear/cytoplasmic fractionation

    PMID:21388963 PMID:21829621 PMID:21937598 PMID:22438573

    Open questions at the time
    • How ISL1 promotes β-catenin nuclear accumulation mechanistically was unexplained
    • Whether ISL1's proliferative targets in islets overlap with oncogenic programs was untested
  10. 2012 High

    Reconstitution of the Isl1–Lhx3 hexameric complex demonstrated it is a potent and specific motor neuron fate determinant that activates motor neuron genes and suppresses interneuron programs; in parallel, ISL1's interaction partners Ldb1 (co-occupying ISL1 targets genome-wide in islets) and CIP (repressing ISL1-driven MEF2C activation) were characterized, revealing the coregulatory logic of ISL1 complexes.

    Evidence Isl1-Lhx3 fusion protein in chick spinal cord and mouse ES cells with RNA-seq; conditional Ldb1 KO phenocopying ISL1 KO plus ChIP; yeast two-hybrid, Co-IP, and reporter assays for CIP

    PMID:22343290 PMID:22343712 PMID:23193182

    Open questions at the time
    • Stoichiometry and structure of the hexamer were not resolved at atomic level
    • How CIP modulates ISL1 activity under hypertrophic stress in vivo was incompletely defined
  11. 2012 High

    Defined the Nkx2-5–ISL1 antagonistic regulatory axis: Nkx2-5 directly represses ISL1 and its target Fgf10 in differentiating ventricular myocardium, while sustained ISL1 expression drives pacemaker/nodal identity, establishing ISL1 dosage as a binary switch between ventricular and conduction-system fates.

    Evidence ChIP showing Nkx2-5 binding to ISL1 enhancer; conditional Nkx2-5 KO; ISL1 gain-of-function with electrophysiological readout; mutagenesis of Fgf10 regulatory element

    PMID:23093675 PMID:25524439

    Open questions at the time
    • How chromatin state at the ISL1 locus transitions from active to repressed during ventricular differentiation was unresolved
    • Whether pharmacological modulation of this switch could reprogram chamber identity was untested
  12. 2013 High

    Revealed ISL1 as a dual-mode transcriptional regulator in the striatum—activating striatonigral (substance P, prodynorphin) and repressing striatopallidal (Drd2, proenkephalin) gene programs—and identified Shox2 as a direct upstream activator of ISL1 in the sinoatrial node.

    Evidence Conditional ISL1 KO in striatum with fate mapping and behavioral analysis; in utero electroporation gain-of-function; EMSA and reporter assays for Shox2 binding ISL1 intron; zebrafish rescue

    PMID:23455426 PMID:24082127 PMID:24351932

    Open questions at the time
    • Direct ISL1 binding sites at striatonigral target genes were not mapped genome-wide
    • Mechanism of transcriptional repression by ISL1 at striatopallidal loci was undefined
  13. 2014 High

    Genome-wide ChIP-seq showed ISL1 assembles distinct hexameric complexes (Isl1–Lhx3 and Isl1–Lhx8) that converge on cholinergic pathway genes in motor and forebrain neurons, while ISL1 was also shown to directly regulate Pdx1 and Glut2 in mature beta-cells for insulin secretion independent of cell mass.

    Evidence ChIP-seq of Isl1–Lhx3 and Isl1–Lhx8; conditional ISL1 KO in forebrain and spinal cord; inducible beta-cell-specific ISL1 KO with ChIP-seq and glucose tolerance testing

    PMID:24763339 PMID:25028525

    Open questions at the time
    • How hexamer composition is regulated by LHX partner availability in vivo was unknown
    • Post-developmental role of ISL1 in adult neural circuits was largely uncharacterized
  14. 2015 High

    Established ISL1 as a central regulator of sinoatrial node pacemaker identity, directly binding and controlling ~one-third of SAN-enriched genes including calcium channel subunits, Tbx3, and Ank2; simultaneously, the Isl1–Lhx3 autoregulatory loop (self-activating Isl1, Lhx3, and Lmo4) was defined as a mechanism that consolidates motor neuron fate.

    Evidence SAN-specific ISL1 conditional KO; FACS-purified SAN ChIP; RNA-seq; ChIP-seq and reporter assays for autoregulatory elements

    PMID:26193633 PMID:26447474 PMID:28451636

    Open questions at the time
    • Whether ISL1 is required for SAN function in the adult heart was not established
    • Structural basis for ISL1 binding specificity at SAN versus motor neuron enhancers was unresolved
  15. 2015 High

    Demonstrated that co-expression of Pou4f2 and ISL1 is sufficient to specify functional retinal ganglion cells even in the absence of Atoh7, establishing the minimal transcription factor code for RGC fate.

    Evidence Binary knockin of Pou4f2 + Isl1 in Atoh7-null retina; electrophysiological recording; gene expression analysis

    PMID:25775587

    Open questions at the time
    • Whether Pou4f2 and ISL1 bind as a physical complex or independently at RGC enhancers was unknown
    • Long-term maintenance and connectivity of rescued RGCs was not fully assessed
  16. 2018 High

    In human ESC cardiac differentiation, ISL1 was shown to accelerate cardiomyocyte differentiation and promote ventricular over atrial identity by antagonizing retinoic acid signaling at NR2F1; in sympathetic neurons, ChIP-seq revealed ISL1 directly controls fate, proliferation, axon growth, and noradrenergic-versus-cholinergic balance.

    Evidence ISL1 KD in human ESC differentiation with transcriptomics; ISL1 hypomorphic mouse and neural crest-specific KO with ChIP-seq and RNA-seq

    PMID:29337667 PMID:29445148

    Open questions at the time
    • Whether ISL1's chamber-specifying role operates through the same pioneer mechanism identified in mouse was untested
    • Relevance of ISL1 sympathetic targets to human neuroblastoma requires clinical validation
  17. 2019 High

    Identified ISL1 as a pioneer transcription factor in cardiac progenitors: ISL1 binds compacted chromatin and recruits the Brg1–Baf60c SWI/SNF complex to establish accessible chromatin at cardiac lineage loci, providing the epigenetic mechanism underlying its fate-determining activity.

    Evidence ChIP-seq, ATAC-seq, and RNA-seq in ISL1-hypomorphic cardiac progenitors; interaction with Brg1–Baf60c complex

    PMID:31024170

    Open questions at the time
    • Whether ISL1 pioneer activity depends on specific DNA motif features or nucleosome positioning was uncharacterized
    • The mechanism of ISL1 recruitment to closed chromatin prior to SWI/SNF engagement was unresolved
  18. 2019 High

    Extended ISL1's developmental repertoire to trachea-esophageal separation through direct transcriptional regulation of Nkx2.1 in midline epithelial progenitors, with human genomic data linking ISL1 locus deletions to tracheo-esophageal malformations.

    Evidence Conditional ISL1 deletion in mice and Xenopus; lineage tracing; human patient genotyping

    PMID:31813798

    Open questions at the time
    • Precise ISL1-binding elements at Nkx2.1 were not mapped
    • Whether other transcription factors cooperate with ISL1 in midline epithelial specification was unknown
  19. 2020 High

    Identification of a SAN-specific ISL1 enhancer whose deletion causes SAN hypoplasia and arrhythmias, with syntenic human SNPs associating with resting heart rate, provided the cis-regulatory mechanism linking ISL1 dosage to pacemaker function and human cardiac rhythm.

    Evidence ATAC-seq on sorted SAN cells; CRISPR enhancer deletion in mouse; transgenic reporters; GWAS association

    PMID:33044128

    Open questions at the time
    • Transcription factors driving activity of this enhancer beyond ISL1 autoregulation were not fully identified
    • Whether enhancer variants causally alter heart rate in humans was not functionally proven
  20. 2022 High

    Conditional ISL1 deletion in auditory spiral ganglion neurons revealed ISL1 governs their formation, migration, axonal wiring, and tonotopic organization, expanding ISL1's sensory neuron roles to the auditory system.

    Evidence Conditional ISL1 KO (Neurod1-Cre); transcriptome analysis; anatomical and electrophysiological analysis

    PMID:36074819

    Open questions at the time
    • Direct ISL1 target genes in spiral ganglion neurons were not mapped by ChIP
    • Whether ISL1 is required for maintenance of auditory neuron function in adulthood was not assessed
  21. 2024 Medium

    Revealed a post-translational regulatory mechanism in endothelial cells: EphrinB2 activates CDK5 which phosphorylates ISL1, driving its nuclear translocation where it binds the VEGFR3 promoter to promote lymphangiogenesis, establishing a non-developmental, injury-responsive ISL1 function.

    Evidence EphrinB2 overexpression/deletion in mouse; subcellular fractionation; ChIP at VEGFR3 promoter; pharmacological VEGFR3 inhibition

    PMID:39557830

    Open questions at the time
    • The specific ISL1 phosphorylation site(s) targeted by CDK5 were not identified
    • Whether CDK5-mediated ISL1 regulation occurs in other cell types is unknown
    • Single-lab finding not yet independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: the atomic structure of ISL1-containing hexameric complexes; the precise mechanism by which ISL1 is recruited to closed chromatin as a pioneer factor; whether ISL1's adult functions in mature neurons and endocrine cells involve ongoing pioneer activity or conventional transcription factor mechanisms; and the full spectrum of human disease caused by ISL1 coding and regulatory variants.
  • No high-resolution structure of any ISL1-containing hexameric complex
  • Pioneer factor mechanism at nucleosome level uncharacterized
  • Comprehensive human genetic studies of ISL1 loss-of-function are lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 11 GO:0003677 DNA binding 5 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 3
Pathway
R-HSA-1266738 Developmental Biology 14 R-HSA-74160 Gene expression (Transcription) 9 R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 5 R-HSA-4839726 Chromatin organization 1
Partners
BETA2HNF4ALDB1LHX3LHX8POU4F2SSBP3TBX20
Complex memberships
Brg1-Baf60c/SWI/SNF complexISL1-Ldb1-SSBP3 complexIsl1-Lhx3 hexamerIsl1-Lhx8 hexamer

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The two LIM domains of ISL1 inhibit DNA binding by the homeodomain in vitro and in vivo; truncation or denaturation/renaturation of the LIM domains relieves this inhibition, and LIM domains from ISL1 can inhibit the homeodomain of an unrelated protein (Ubx), demonstrating a general cis-inhibitory mechanism. In vitro DNA binding assays with bacterially expressed proteins, truncation mutants, and in vivo reporter assays The EMBO journal High 7901000
1997 ISL1 is required cell-autonomously in pancreatic endodermal cells for the generation of all endocrine islet cells, and is also required in dorsal mesenchymal cells for formation of dorsal pancreatic mesenchyme (and thereby for dorsal exocrine differentiation); provision of wild-type mesenchyme rescues exocrine but not endocrine differentiation in ISL1-null explants. ISL1 knockout mice analyzed by histology; in vitro mesenchyme rescue experiments Nature High 9000074
2000 ISL1 directly interacts in vivo and in vitro with the estrogen receptor (ER); interaction is mediated by the ER ligand-binding domain and is strengthened by estradiol; ISL1 prevents ER dimerization and inhibits ER DNA-binding activity; ISL1 LIM domains specifically inhibit ER-driven transcription in some promoter contexts, while ER can coactivate ISL1 in others. Co-immunoprecipitation (in vivo), GST pulldown (in vitro), dual immunohistochemistry, gel shift (EMSA), reporter assays Molecular endocrinology High 11043578
2007 Beta-catenin (Wnt/β-catenin pathway) directly regulates the ISL1 promoter in cardiovascular progenitors; ablation of beta-catenin in ISL1-expressing progenitors abolishes ISL1 expression and disrupts cardiogenesis, demonstrating beta-catenin is genetically upstream of ISL1. ChIP demonstrating beta-catenin occupancy of Isl1 promoter; conditional beta-catenin knockout in ISL1-Cre lineage with phenotypic analysis Proceedings of the National Academy of Sciences of the United States of America High 17519333
2007 Wnt/β-catenin signaling promotes renewal and inhibits differentiation of ISL1+ cardiovascular progenitors; in vivo activation of β-catenin in ISL1+ cells causes their massive accumulation and OFT defects; deletion of β-catenin in ISL1+ cells reduces mitosis; the microenvironment can be reconstituted by a Wnt3a-secreting feeder layer. Genetic gain- and loss-of-function of β-catenin in ISL1-Cre mouse; ES cell and embryonic ISL1+ progenitor culture with Wnt3a feeder layer Cell stem cell High 18371348
2007 Wnt/β-catenin signaling in ISL1+ anterior heart field (AHF) progenitors promotes their expansion through upregulation of specific FGF ligands (Fgf3, Fgf10, Fgf16, Fgf20); loss of Wnt signaling in AHF reduces ISL1+ progenitors and FGF signaling; gain of Wnt increases both. Conditional Wnt loss- and gain-of-function in ISL1-Cre mouse; gene expression analysis; definition of Wnt-FGF signaling axis The Journal of clinical investigation High 17607356
2008 Conditional knockout of ISL1 in the developing retina causes apoptosis of retinal ganglion cells (RGCs); Isl1 controls a distinct set of downstream genes (identified by microarray) that are downstream of Math5 and partly overlap with but are distinct from Pou4f2 targets; Isl1 positively regulates Pou4f2 expression. Conditional ISL1 knockout in retina (Cre/loxP); microarray; histology and apoptosis assays Proceedings of the National Academy of Sciences of the United States of America High 18460603
2008 Conditional knockout of ISL1 in sensory neurons causes loss of nociceptive marker TrkA and Runx1, near-absence of cutaneous innervation, and prolonged expression of early developmental regulators; later ISL1 excision reduces transcripts related to specific sensory functions without reactivating early genes, establishing ISL1 as central to the transition from sensory neurogenesis to subtype specification. Conditional ISL1 knockout strategies (early and late); microarray analysis of mutant ganglia; immunohistochemistry Nature neuroscience High 18849985
2008 Notch1 positively, and β-catenin negatively, regulate ISL1 expression in cardiac progenitor cells (CPCs); disruption of ISL1 in CPCs leads to their expansion in vivo and in ES cells; ISL1 is required for CPC differentiation into cardiomyocytes and smooth muscle cells, but not endothelial cells. Conditional Notch1 and β-catenin genetic manipulation in CPCs; Isl1 conditional knockout; ES cell assays Nature cell biology High 19620969
2009 ISL1 synergistically activates insulin gene transcription with BETA2; protein-protein interaction between ISL1 and BETA2 is mediated by the LIM domains of ISL1 and the bHLH domain of BETA2; deletion of both LIM domains enhances transcriptional activation of the insulin gene, revealing the homeodomain as the primary transactivating domain; ISL1 binds the A3/4 box of the rat insulin I promoter through its homeodomain. Co-immunoprecipitation; deletion mutant luciferase reporter assays; EMSA (gel shift) with homeodomain binding Journal of molecular biology High 19619559
2009 ISL1-deficient endocrine precursors fail to mature into functional islet cells; MafA is identified as a direct transcriptional target of ISL1 in pancreatic islet cells. Conditional ISL1 deletion in pancreatic epithelium (Cre/loxP from E13.5); ChIP; gene expression analysis Diabetes High 19502415
2011 ISL1 directly binds the promoters of c-Myc and CyclinD1 to activate their transcription, thereby promoting adult pancreatic islet cell proliferation; knockdown of ISL1 increases apoptosis and causes G1 arrest in pancreatic islet cells. ChIP assay; luciferase reporter assays; ISL1 knockdown with cell cycle and apoptosis analysis PloS one Medium 21829621
2011 Isl1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory pathway; conditional inactivation of Isl1 in hindlimb-forming region causes downregulation of Hand2 and severe impairment of Shh expression specifically in the hindlimb, but not the forelimb. Conditional ISL1 knockout using Hoxb6Cre; in situ hybridization; phenotypic analysis of limb development Development (Cambridge, England) High 22438573
2011 ISL1 is required for nuclear accumulation of β-catenin and activation of the β-catenin pathway in the lateral plate mesoderm; β-catenin in turn maintains ISL1 expression; together they act upstream of Fgf10 to regulate hindlimb outgrowth. Conditional ISL1 and β-catenin knockout in lateral plate mesoderm; nuclear/cytoplasmic fractionation; gene expression analysis Development (Cambridge, England) High 21937598
2011 Isl-1 regulates Arx transcription in pancreatic islet alpha-cells by directly binding two conserved noncoding regulatory regions (Re1 and Re2) in the Arx locus; ISL1 is the first known transcriptional activator of Arx in alpha-cells. ChIP localization of ISL1 binding sites; luciferase reporter assays; ISL1 overexpression and knockdown; site-directed mutation experiments The Journal of biological chemistry High 21388963
2012 Ldb1 is the primary coregulator of ISL1 in developing and adult islet cells; endocrine cell-specific removal of Ldb1 phenocopies ISL1 conditional knockout; ChIP analysis shows Ldb1 co-occupies ISL1 target gene promoters (MafA, Arx, insulin, Glp1r) alongside ISL1. Conditional Ldb1 knockout (Cre/loxP); ChIP; gene expression analysis Diabetes High 23193182
2012 The Drosophila ISL1 ortholog Tailup (Tup) functions in cardiac specification upstream of Tin, Pnr and Dorsocross; tup cooperates with these cardiac transcription factors in heart cell specification; Tup in ectoderm regulates cardiogenesis via distinct LIM-domain-interacting proteins from those in mesoderm. tup mutant analysis; genetic interaction studies; germ layer-specific loss-of-function and rescue experiments; gain-of-function analyses in Drosophila Development (Cambridge, England) Medium 19088091
2012 Nkx2-5 directly binds to an ISL1 enhancer and represses ISL1 transcriptional activity; this direct repression of ISL1 by Nkx2-5 is necessary for proper development of the ventricular myocardial lineage; overexpression of ISL1 shifts cardiomyocyte identity toward nodal/pacemaker subtype at the expense of ventricular identity. ChIP showing Nkx2-5 binding to ISL1 enhancer; conditional Nkx2-5 KO in ISL1+ lineage; ISL1 overexpression in mouse ESCs and Xenopus embryos; electrophysiology Stem cells (Dayton, Ohio) High 25524439
2012 ISL1 directly regulates Fgf10 gene expression in the anterior second heart field by binding to a 1.7-kb intronic regulatory element; this is antagonized by Nkx2-5, which represses Fgf10 (and ISL1 expression) in differentiating myocardium. Transgenic reporter assays; ChIP demonstrating direct ISL1 binding; gain- and loss-of-function genetic backgrounds; site-directed mutagenesis of regulatory element Proceedings of the National Academy of Sciences of the United States of America High 23093675
2012 CIP (cardiac ISL1-interacting protein) directly interacts with ISL1 and represses ISL1's transcriptional activity on MEF2C; CIP overexpression represses agonist-induced cardiomyocyte hypertrophy; CIP expression is reduced in hypertrophic cardiomyocytes. Yeast two-hybrid screening; Co-IP; domain mapping; luciferase reporter assays; CIP overexpression in cardiomyocyte hypertrophy model Circulation research High 22343712
2012 ISL1 and Lhx3 form a hexameric complex (Isl1-Lhx3-hexamer) in spinal motor neurons that is a potent and specific inducer of motor neuron fate; an equimolar ratio of Isl1:Lhx3 and the LIM domain of Lhx3 are critical; the Isl1-Lhx3 fusion protein drives motor neuron transcriptome and suppresses interneuron programs. Isl1-Lhx3 fusion protein expression in chick spinal cord and mouse ES cells; RNA-seq; suppression of interneuron gene expression Proceedings of the National Academy of Sciences of the United States of America High 22343290
2013 ISL1 is required for correct development of the striatonigral (direct) pathway in the striatum; conditional ISL1 inactivation results in fewer striatonigral neurons, reduced substantia nigra projections, and involvement of PlexinD1-Semaphorin 3e signaling in diencephalic cells bordering the internal capsule; ISL1 conditional mutants show hyperlocomotion and blunted response to psychostimulants. Conditional ISL1 knockout in telencephalon and ventral forebrain; genetic fate mapping; behavioral analysis; axon projection analysis Proceedings of the National Academy of Sciences of the United States of America High 24082127
2013 ISL1 specifies striatonigral neuron identity by a dual mechanism: promoting striatonigral gene expression (substance P, prodynorphin, PlexinD1) and simultaneously repressing striatopallidal genes (Drd2, proenkephalin, A2aR, Gpr6); ectopic ISL1 expression in striatopallidal neurons is sufficient to repress Drd2-EGFP. Conditional ISL1 knockout; in utero electroporation for ISL1 overexpression; Drd2-EGFP transgenic mice; gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 24351932
2013 Shox2 directly transcriptionally activates ISL1 in the sinoatrial node through two specific SHOX2-binding sites within intron 2 of the ISL1 locus; overexpression of ISL1 rescues the bradycardia phenotype caused by Shox2 knockdown in zebrafish. Luciferase reporter assays; EMSA; microarray/gene expression analysis; zebrafish rescue experiment Basic research in cardiology High 23455426
2013 Leptin suppresses ISL1 expression and insulin secretion via JAK-STAT3 signaling; ISL1 is a direct downstream target of STAT3; the effect of leptin on insulin secretion is lost in Isl1-inducible knockout mice. In vivo and in vitro leptin treatment; Isl1-inducible knockout mouse model; gene expression analysis The Journal of biological chemistry Medium 23504315
2014 ISL1 forms two related but distinct hexameric complexes — Isl1-Lhx3-hexamer in spinal motor neurons and Isl1-Lhx8-hexamer in forebrain cholinergic neurons — that both bind and activate a suite of cholinergic pathway genes (acetylcholine synthesizing enzymes and transporters) to specify cholinergic neuronal identity; conditional ISL1 inactivation causes loss of cholinergic neurons in both regions. Conditional ISL1 KO in spinal cord and forebrain; genome-wide ChIP-seq of Isl1-Lhx3 and Isl1-Lhx8 complexes; luciferase reporter assays; ES cell differentiation PLoS genetics High 24763339
2014 ISL1 directly occupies regulatory elements of Pdx1 and Slc2a2 (Glut2) in postnatal beta-cells (ChIP-seq and luciferase reporter assays); postnatal beta-cell-specific ablation of ISL1 impairs insulin secretion without reducing beta-cell mass, demonstrating a distinct function for ISL1 in mature beta-cell function. Tamoxifen-inducible beta-cell-specific ISL1 knockout; ChIP-seq; luciferase reporter assays; glucose tolerance and insulin secretion assays Diabetes High 25028525
2014 ISL1 directly targets Gata3 to regulate pyloric development; ISL1 deficiency leads to near-complete absence of the pyloric outer longitudinal muscle layer; ISL1 binding to and transactivation of the Gata3 locus demonstrated by ChIP, luciferase assays, and EMSA. Tamoxifen-inducible ISL1 knockout; ChIP; luciferase reporter assays; EMSA BMC biology High 24674670
2015 ISL1 is essential for survival, proliferation, and function of sinoatrial node (SAN) pacemaker cells; ChIP with anti-ISL1 antibodies on FACS-purified SAN cells shows ISL1 directly binds genomic regions of L-type calcium channel subunit genes, Ank2, and Tbx3; RNA-seq identifies ISL1 as regulating ~one-third of SAN-specific genes. SAN-specific ISL1 conditional KO; FACS-purified SAN cells; RNA-seq; ChIP on purified pacemaker cells The Journal of clinical investigation High 26193633
2015 Two transcription factors, Pou4f2 and ISL1, are jointly sufficient to specify the RGC fate; ectopic expression of both in Atoh7-null retina (which lacks RGCs) produces largely normal RGCs that survive to postnatal stages and are physiologically functional. Binary knockin-transgenic system for ectopic Pou4f2+Isl1 expression in Atoh7-null retina; electrophysiological recording; gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 25775587
2015 The Isl1-Lhx3 complex activates transcription of Isl1, Lhx3, and Lmo4 genes through direct binding to specific genomic loci, establishing a potent autoregulatory feedback loop; LMO4 produced by this loop blocks V2 interneuron-specifying Lhx3 complex, increasing Lhx3 available for the Isl1-Lhx3 complex. Genome-wide ChIP-seq; reporter assays in chick neural tube and mouse embryos; gain- and loss-of-function experiments eNeuro High 28451636
2015 ISL1 expression in motor neurons is controlled by two distinct enhancers (CREST1/E1 and CREST2/E2): E1 is bound by Phox2 proteins (hindbrain) and by the Isl1-Lhx3 complex (spinal cord); E2 is activated by OC-1 in lateral motor column neurons innervating limb muscles; E2 is only found in tetrapods. Genome-wide ChIP-seq; GFP reporter assays in chick neural tube; comparative genomics; overexpression and binding assays PLoS genetics High 26447474
2015 SSBP3 interacts with both Ldb1 and ISL1 in beta-cells (identified by cross-linked IP and mass spectrometry; confirmed by Co-IP in beta-cell lines and mouse/human islets); SSBP3 knockdown causes mRNA deficiencies at Ldb1-Isl1 target promoters (MafA, Glp1r), and SSBP3 occupies these promoters. Cross-linked immunoprecipitation + mass spectrometry; Co-IP; ChIP; SSBP3 knockdown gene expression analysis Molecular endocrinology High 26495868
2018 In human ESC-based cardiac differentiation, ISL1 does not stabilize the cardiac precursor state but accelerates cardiomyocyte differentiation; ISL1 depletion delays cardiac differentiation and respecifies nascent cardiomyocytes from ventricular to atrial identity; ISL1 is antagonized by retinoic acid signaling via MEIS2, and ISL1 competes with the retinoic acid pathway at the atrial specifier NR2F1. ISL1 depletion in human ESC cardiac differentiation; transcriptome analysis; mechanistic analysis of retinoic acid/MEIS2/NR2F1 pathway interactions eLife Medium 29337667
2018 ISL1 is required during sympathetic neuron development for fate determination, differentiation, repression of glial differentiation, proliferation (via cell cycle gene control), axon growth, and maintenance of noradrenergic (while repressing cholinergic) differentiation; ChIP-seq identifies direct ISL1 target genes including several implicated in neuroblastoma pathogenesis. Isl1 hypomorphic mouse line and neural crest-specific Isl1 knockout; RNA-seq; ISL1 ChIP-seq on sympathetic ganglia Cell death & disease High 29445148
2019 ISL1 acts as a pioneer transcription factor in cardiac progenitor cells, binding to compacted chromatin; ISL1 works in concert with the Brg1-Baf60c-based SWI/SNF complex to establish permissive chromatin at cardiac lineage-specific loci (including both progenitor genes and cardiomyocyte structural genes), thereby establishing epigenetic memory of cardiomyocyte fate commitment. ISL1 hypomorphic mouse; genome-wide ISL1 binding (ChIP-seq); ATAC-seq; RNA-seq in cardiac progenitors; interaction with Brg1-Baf60c SWI/SNF complex Cell research High 31024170
2019 ISL1 regulates Nkx2.1 transcription in midline epithelial cells (MECs, an ISL1+Nkx2.1+Sox2+ progenitor population) to orchestrate trachea-esophageal separation; lineage tracing shows MECs contribute to both tracheal and esophageal epithelium; deletion of the chromosomal region spanning ISL1 is found in human patients with tracheo-esophageal defects. Conditional ISL1 deletion in mice and Xenopus; Cre-based lineage tracing; gene expression analysis (Nkx2.1); human patient genotyping Developmental cell High 31813798
2020 A 2.9-kb cis-regulatory enhancer at the ISL1 locus is specifically active in the cardiac inflow/SAN from E8.5 through SAN maturation; deletion of this enhancer causes SAN hypoplasia and sinus arrhythmias; SNPs near the syntenic human ISL1 enhancer associate with resting heart rate in GWAS. ATAC-seq on sorted SAN cells; transgenic reporter mice; enhancer deletion by CRISPR; zebrafish reporter assay Circulation research High 33044128
2006 ISL1 interacts with HNF4alpha through the HNF4alpha AF-2 and F domains; ISL1 homeodomain and first LIM domain mediate the interaction; together they synergistically activate transcription of HNF1alpha, PPARalpha, and insulin I promoters; ISL1 can also recruit the cofactor CLIM2 to further enhance transcription. Co-immunoprecipitation; GST pulldown; domain mapping with deletion mutants; luciferase reporter assays; ChIP showing increased HNF4alpha loading Journal of molecular biology High 17022998
2003 An alternatively spliced ISL1 isoform (ISL1-beta), lacking the C-terminal 23 amino acids, is a more potent transactivator of the insulin promoter than ISL1-alpha; ISL1-alpha undergoes phosphorylation, indicating post-translational regulation; both isoforms localize to the nucleus. cDNA cloning; transient transfection reporter assays; immunofluorescence localization; phosphorylation analysis Journal of molecular endocrinology Medium 14664703
2018 ISL1 loss-of-function mutations (nonsense mutations causing truncation) abolish ISL1 transcriptional activity on the MEF2C promoter and nullify synergistic activation with TBX20, linking ISL1 mutations to congenital heart defects in humans. Sanger sequencing of CHD patients; dual-luciferase reporter assay Heart and vessels Medium 30390123
2019 A novel ISL1 loss-of-function nonsense mutation (p.Tyr75*) abolishes ISL1 transcriptional activity and nullifies synergistic activation with TBX20 on the MEF2C promoter, and co-segregates with double outlet right ventricle in a family. Sanger sequencing; dual-luciferase reporter assay International heart journal Low 31484864
2017 ISL1 regulates multiple signaling pathways (BMP, WNT, FGF) during external genitalia development; ChIP-seq identifies ISL1 targets including Bmp4, Fgf10, and Wnt5a; an essential function of ISL1 is to induce Bmp4-mediated apoptosis in genital mesenchyme; ISL1 deletion in genital mesenchyme causes epispadias-like phenotype and hydroureter. Conditional ISL1 knockout in genital mesenchyme; ChIP-seq; expression analysis; apoptosis assays Human molecular genetics High 29126155
2022 ISL1 regulates molecular and cellular features of spiral ganglion (auditory) neurons including formation, migration, peripheral and central axonal wiring, and tonotopic organization; ISL1-knockout spiral ganglion neurons migrate ectopically and lose topographic projections; transcriptome analysis shows ISL1 regulates neurogenesis, axonogenesis, migration, neurotransmission, and synaptic communication. Conditional ISL1 knockout in spiral ganglion neurons (Neurod1-Cre); transcriptome analysis; anatomical and electrophysiological analysis of auditory pathway Proceedings of the National Academy of Sciences of the United States of America High 36074819
2024 EphrinB2 promotes cardiac lymphatic endothelial cell proliferation and migration by activating CDK5, which phosphorylates and causes nuclear translocation of ISL1; nuclear ISL1 then enhances transcription of VEGFR3 (FLT4) by binding its promoter, driving lymphangiogenesis after myocardial infarction. EphrinB2 overexpression/deletion in mice; subcellular fractionation (nuclear translocation); ChIP/promoter binding assay for ISL1 at VEGFR3 promoter; VEGFR3 inhibitor pharmacology Signal transduction and targeted therapy Medium 39557830

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Independent requirement for ISL1 in formation of pancreatic mesenchyme and islet cells. Nature 575 9000074
2009 Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature 413 19571884
2007 The renewal and differentiation of Isl1+ cardiovascular progenitors are controlled by a Wnt/beta-catenin pathway. Cell stem cell 253 18371348
1994 Developmental regulation of islet-1 mRNA expression during neuronal differentiation in embryonic zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists 213 8167375
2007 Wnt/beta-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling. The Journal of clinical investigation 212 17607356
2007 Beta-catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis. Proceedings of the National Academy of Sciences of the United States of America 194 17519333
2008 Islet1 cardiovascular progenitors: a single source for heart lineages? Development (Cambridge, England) 191 18156162
2009 A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nature cell biology 186 19620969
2008 A central role for Islet1 in sensory neuron development linking sensory and spinal gene regulatory programs. Nature neuroscience 168 18849985
2007 Islet-1 controls the differentiation of retinal bipolar and cholinergic amacrine cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 156 18003851
2008 The contribution of Islet1-expressing splanchnic mesoderm cells to distinct branchiomeric muscles reveals significant heterogeneity in head muscle development. Development (Cambridge, England) 141 18184728
2008 Gene regulation logic in retinal ganglion cell development: Isl1 defines a critical branch distinct from but overlapping with Pou4f2. Proceedings of the National Academy of Sciences of the United States of America 127 18460603
2008 Nkx2-5- and Isl1-expressing cardiac progenitors contribute to proepicardium. Biochemical and biophysical research communications 115 18722343
2009 Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreas. Diabetes 111 19502415
2004 Expression of Islet1 marks the sensory and neuronal lineages in the mammalian inner ear. The Journal of comparative neurology 110 15329890
1993 The cysteine-rich LIM domains inhibit DNA binding by the associated homeodomain in Isl-1. The EMBO journal 107 7901000
2006 Islet1 and Islet2 have equivalent abilities to promote motoneuron formation and to specify motoneuron subtype identity. Development (Cambridge, England) 99 16672347
2015 Transcription factor ISL1 is essential for pacemaker development and function. The Journal of clinical investigation 97 26193633
1995 Molecular heterogeneity among primary motoneurons and within myotomes revealed by the differential mRNA expression of novel islet-1 homologs in embryonic zebrafish. Developmental biology 97 7556938
2015 RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells. Circulation research 96 25623957
2013 ISL1 expression is not restricted to pancreatic well-differentiated neuroendocrine neoplasms, but is also commonly found in well and poorly differentiated neuroendocrine neoplasms of extrapancreatic origin. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 93 23503646
2012 Fibroblast growth factor 10 gene regulation in the second heart field by Tbx1, Nkx2-5, and Islet1 reveals a genetic switch for down-regulation in the myocardium. Proceedings of the National Academy of Sciences of the United States of America 93 23093675
2015 Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate. Proceedings of the National Academy of Sciences of the United States of America 91 25775587
2013 Driving vascular endothelial cell fate of human multipotent Isl1+ heart progenitors with VEGF modified mRNA. Cell research 88 24018375
2014 Isl1 directly controls a cholinergic neuronal identity in the developing forebrain and spinal cord by forming cell type-specific complexes. PLoS genetics 85 24763339
2003 Role of Islet1 in the patterning of murine dentition. Development (Cambridge, England) 79 12900460
2019 Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate. Cell research 78 31024170
2013 Nkx2-5(+)islet1(+) mesenchymal precursors generate distinct spleen stromal cell subsets and participate in restoring stromal network integrity. Immunity 72 23601687
2014 Islet-1 Is essential for pancreatic β-cell function. Diabetes 71 25028525
2015 Direct nkx2-5 transcriptional repression of isl1 controls cardiomyocyte subtype identity. Stem cells (Dayton, Ohio) 69 25524439
2011 ISL1 promotes pancreatic islet cell proliferation. PloS one 69 21829621
2006 Multipotential nestin and Isl-1 positive mesenchymal stem cells isolated from human pancreatic islets. Biochemical and biophysical research communications 68 16713999
2010 Common variation in ISL1 confers genetic susceptibility for human congenital heart disease. PloS one 67 20520780
2019 Isl1-expressing non-venous cell lineage contributes to cardiac lymphatic vessel development. Developmental biology 66 31112709
2013 Islet1 is a direct transcriptional target of the homeodomain transcription factor Shox2 and rescues the Shox2-mediated bradycardia. Basic research in cardiology 66 23455426
2012 Fusion protein Isl1-Lhx3 specifies motor neuron fate by inducing motor neuron genes and concomitantly suppressing the interneuron programs. Proceedings of the National Academy of Sciences of the United States of America 65 22343290
2005 Retinaldehyde dehydrogenase 2 and Hoxc8 are required in the murine brachial spinal cord for the specification of Lim1+ motoneurons and the correct distribution of Islet1+ motoneurons. Development (Cambridge, England) 64 15753214
2013 The LIM homeobox gene Isl1 is required for the correct development of the striatonigral pathway in the mouse. Proceedings of the National Academy of Sciences of the United States of America 61 24082127
2013 Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity. Proceedings of the National Academy of Sciences of the United States of America 60 24351932
2008 Islet1 as a marker of subdivisions and cell types in the developing forebrain of Xenopus. Neuroscience 59 18515014
2022 Islet-1 Mesenchymal Stem Cells-Derived Exosome-Incorporated Angiogenin-1 Hydrogel for Enhanced Acute Myocardial Infarction Therapy. ACS applied materials & interfaces 55 35920579
2004 Islet-1 expression in the developing chicken inner ear. The Journal of comparative neurology 53 15281076
2012 Islet1 regulates establishment of the posterior hindlimb field upstream of the Hand2-Shh morphoregulatory gene network in mouse embryos. Development (Cambridge, England) 50 22438573
2009 The LIM-homeodomain protein ISL1 activates insulin gene promoter directly through synergy with BETA2. Journal of molecular biology 50 19619559
2015 Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer. PloS one 48 26332997
2011 Islet1-mediated activation of the β-catenin pathway is necessary for hindlimb initiation in mice. Development (Cambridge, England) 48 21937598
2020 ATAC-Seq Reveals an Isl1 Enhancer That Regulates Sinoatrial Node Development and Function. Circulation research 47 33044128
2020 Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin. Endocrine pathology 45 32813226
2000 The LIM/homeodomain protein islet-1 modulates estrogen receptor functions. Molecular endocrinology (Baltimore, Md.) 42 11043578
2019 Isl1 Regulation of Nkx2.1 in the Early Foregut Epithelium Is Required for Trachea-Esophageal Separation and Lung Lobation. Developmental cell 41 31813798
2018 Revised roles of ISL1 in a hES cell-based model of human heart chamber specification. eLife 40 29337667
2012 Islet α-, β-, and δ-cell development is controlled by the Ldb1 coregulator, acting primarily with the islet-1 transcription factor. Diabetes 38 23193182
2007 Biology of Isl1+ cardiac progenitor cells in development and disease. Cellular and molecular life sciences : CMLS 38 17380308
2018 Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification. Cell death & disease 35 29445148
2015 Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy. PLoS genetics 35 25763902
2008 The Drosophila homolog of vertebrate Islet1 is a key component in early cardiogenesis. Development (Cambridge, England) 35 19088091
2022 ISL1 is necessary for auditory neuron development and contributes toward tonotopic organization. Proceedings of the National Academy of Sciences of the United States of America 33 36074819
2007 Nkx6 proteins specify one zebrafish primary motoneuron subtype by regulating late islet1 expression. Development (Cambridge, England) 33 17376808
2014 Comparative expression analysis of POU4F1, POU4F2 and ISL1 in developing mouse cochleovestibular ganglion neurons. Gene expression patterns : GEP 32 24709358
2011 Islet-1 regulates Arx transcription during pancreatic islet alpha-cell development. The Journal of biological chemistry 32 21388963
2014 Impaired enteroendocrine development in intestinal-specific Islet1 mouse mutants causes impaired glucose homeostasis. American journal of physiology. Gastrointestinal and liver physiology 31 25214396
2013 Hair cell overexpression of Islet1 reduces age-related and noise-induced hearing loss. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 24048839
2018 MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats. Journal of cellular physiology 30 30341898
2010 prdm1a Regulates sox10 and islet1 in the development of neural crest and Rohon-Beard sensory neurons. Genesis (New York, N.Y. : 2000) 30 20836130
2012 CIP, a cardiac Isl1-interacting protein, represses cardiomyocyte hypertrophy. Circulation research 29 22343712
2009 Identification of regulatory elements in the Isl1 gene locus. The International journal of developmental biology 29 19598113
2009 A potential role for islet-1 in post-natal angiogenesis and vasculogenesis. Thrombosis and haemostasis 29 20062933
1994 Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected]. Diabetes 29 7912209
2017 ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development. Scientific reports 26 28176844
2017 Transplantation of Isl1+ cardiac progenitor cells in small intestinal submucosa improves infarcted heart function. Stem cell research & therapy 26 29037258
2013 miR-128 regulates non-myocyte hyperplasia, deposition of extracellular matrix and Islet1 expression during newt cardiac regeneration. Developmental biology 26 24055866
2012 Tup/Islet1 integrates time and position to specify muscle identity in Drosophila. Development (Cambridge, England) 25 22949613
2021 The Impact of Spaceflight and Microgravity on the Human Islet-1+ Cardiovascular Progenitor Cell Transcriptome. International journal of molecular sciences 23 33808224
2019 Value of SATB2, ISL1, and TTF1 to differentiate rectal from other gastrointestinal and lung well-differentiated neuroendocrine tumors. Pathology, research and practice 23 31133441
2018 Isl1 mediates mesenchymal expansion in the developing external genitalia via regulation of Bmp4, Fgf10 and Wnt5a. Human molecular genetics 23 29126155
2008 Expression of Islet1 in thyroid development related to budding, migration, and fusion of primordia. Developmental dynamics : an official publication of the American Association of Anatomists 23 18985716
2024 EphrinB2-mediated CDK5/ISL1 pathway enhances cardiac lymphangiogenesis and alleviates ischemic injury by resolving post-MI inflammation. Signal transduction and targeted therapy 22 39557830
2016 CITED2 Cooperates with ISL1 and Promotes Cardiac Differentiation of Mouse Embryonic Stem Cells. Stem cell reports 22 27818139
2013 Islet1 deletion causes kidney agenesis and hydroureter resembling CAKUT. Journal of the American Society of Nephrology : JASN 22 23641053
2020 microRNA-9 and -29a regulate the progression of diabetic peripheral neuropathy via ISL1-mediated sonic hedgehog signaling pathway. Aging 21 32544883
2019 A New ISL1 Loss-of-Function Mutation Predisposes to Congenital Double Outlet Right Ventricle. International heart journal 21 31484864
2018 Prospective Isolation of ISL1+ Cardiac Progenitors from Human ESCs for Myocardial Infarction Therapy. Stem cell reports 21 29503094
2017 The Isl1-Lhx3 Complex Promotes Motor Neuron Specification by Activating Transcriptional Pathways that Enhance Its Own Expression and Formation. eNeuro 21 28451636
2015 Functional Diversification of Motor Neuron-specific Isl1 Enhancers during Evolution. PLoS genetics 21 26447474
2018 ISL1 loss-of-function mutation contributes to congenital heart defects. Heart and vessels 20 30390123
2020 Identifying Isl1 Genetic Lineage in the Developing Olfactory System and in GnRH-1 Neurons. Frontiers in physiology 19 33192618
2019 Adult islet1 Expression Outlines Ventralized Derivatives Along Zebrafish Neuraxis. Frontiers in neuroanatomy 19 30863287
2015 SSBP3 Interacts With Islet-1 and Ldb1 to Impact Pancreatic β-Cell Target Genes. Molecular endocrinology (Baltimore, Md.) 19 26495868
2018 ISL1 promotes cancer progression and inhibits cisplatin sensitivity in triple-negative breast cancer cells. International journal of molecular medicine 18 30226569
2018 The expression of TTF1, CDX2 and ISL1 in 74 poorly differentiated neuroendocrine carcinomas. Annals of diagnostic pathology 18 30236546
2017 Islet-1 induces the differentiation of mesenchymal stem cells into cardiomyocyte-like cells through the regulation of Gcn5 and DNMT-1. Molecular medicine reports 18 28447752
2017 Isl1 Controls Patterning and Mineralization of Enamel in the Continuously Renewing Mouse Incisor. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 18 28650075
2020 Trajectory mapping of human embryonic stem cell cardiogenesis reveals lineage branch points and an ISL1 progenitor-derived cardiac fibroblast lineage. Stem cells (Dayton, Ohio) 17 32497389
2021 Spotlight on Isl1: A Key Player in Cardiovascular Development and Diseases. Frontiers in cell and developmental biology 16 34901033
2014 Wnt-promoted Isl1 expression through a novel TCF/LEF1 binding site and H3K9 acetylation in early stages of cardiomyocyte differentiation of P19CL6 cells. Molecular and cellular biochemistry 16 24610003
2014 LIM homeodomain transcription factor Isl1 directs normal pyloric development by targeting Gata3. BMC biology 16 24674670
2013 LIM-homeodomain transcription factor Isl-1 mediates the effect of leptin on insulin secretion in mice. The Journal of biological chemistry 16 23504315
2012 Elevation of transcription factor Islet-1 levels in vivo increases β-cell function but not β-cell mass. Islets 16 22595886
2006 Hepatocyte nuclear factor 4 alpha ligand binding and F domains mediate interaction and transcriptional synergy with the pancreatic islet LIM HD transcription factor Isl1. Journal of molecular biology 16 17022998
2003 Isolation and characterization of an alternatively spliced variant of transcription factor Islet-1. Journal of molecular endocrinology 16 14664703