Affinage

NEUROD1

Neurogenic differentiation factor 1 · UniProt Q13562

Length
356 aa
Mass
39.9 kDa
Annotated
2026-06-10
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEUROD1 is a class II basic helix-loop-helix transcription factor that functions as a master determinant of neuronal and endocrine differentiation, capable of converting non-neural cells into neurons and driving terminal differentiation programs (PMID:7754368). It binds E-box sequences as a heterodimer with the ubiquitous bHLH partner E47, a configuration defined by the crystal structure of the E47-NEUROD1 bHLH domain on the insulin promoter E-box, in which NEUROD1 homodimer instability favors heterodimer formation (PMID:18069799). NEUROD1 acts as a pioneer factor: it directly occupies epigenetically silenced regulatory elements—including bivalent H3K4me3/H3K27me3 chromatin—and reprograms heterochromatin to euchromatin to establish transcriptional competence at neuronal genes, while inducing repressors that erase alternative cell-fate signatures, and these epigenetic changes persist beyond transient NEUROD1 induction (PMID:26516211, PMID:30638745). Its activity is shaped by partner transcription factors and coactivators, including the SWI/SNF subunit Brg1 required for NEUROD1-driven neuronal differentiation (PMID:15576411), Tcf12 with which it co-occupies target loci to drive cortical neuronal migration (PMID:35147187), the Insm1/Foxa2 combinatorial module governing beta-cell maturity (PMID:25828096), and BET proteins (BRD2/3/4) that act as coactivators in small-cell lung cancer (PMID:36378541). NEUROD1 transcriptional output is gated post-translationally by CaMKII phosphorylation at Ser336, which stimulates its activity and drives activity-dependent dendritogenesis (PMID:14741104), and by MAPK/ERK-dependent nuclear translocation through Ser274 in response to glucose (PMID:12297313); it is antagonized by INSM1-cyclin D1-HDAC repressor complexes at its own promoter (PMID:16569215), by Id2 sequestration of E47 (PMID:12526101), and by c-Myc competition for E-box binding (PMID:11799123). In the pancreas, NEUROD1 is required for islet morphogenesis, endocrine lineage commitment, beta-cell maturation, perinatal proliferation, and glucose-responsive insulin secretion including K(ATP)/SUR1 channel function (PMID:9308961, PMID:20374962, PMID:11981044, PMID:31519700). In the nervous system it controls retinal and inner-ear cell-fate specification, neuronal survival, dendritic and axonal morphogenesis, and migration (PMID:9834183, PMID:11861467, PMID:20512592, PMID:20661473). NEUROD1 also drives malignant programs in neuroendocrine cancers, regulating MYC, TrkB, and NCAM in SCLC and the pentose phosphate enzyme G6PD in colorectal cancer (PMID:23553831, PMID:27452466, PMID:34657129).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Established NEUROD1 as a neuronal determination factor by showing it is sufficient to drive ectopic neuron formation, defining the central question of how a single bHLH factor commits cells to neuronal fate.

    Evidence Ectopic gain-of-function expression in Xenopus embryos with morphological and molecular readout

    PMID:7754368

    Open questions at the time
    • Did not define the genomic targets or chromatin context underlying the conversion
    • Did not address endogenous requirement
  2. 1997 High

    Defined an essential endogenous requirement for NEUROD1 beyond neurons, showing it is needed for beta-cell terminal differentiation and islet morphogenesis, revealing a shared neuroendocrine differentiation role.

    Evidence Knockout mice with histology and immunocytochemistry; corticotroph POMC E-box studies with Co-IP, EMSA, reporter assays

    PMID:9308961 PMID:9343431

    Open questions at the time
    • Did not identify the full beta-cell target gene network
    • Mechanism of maturation versus initial specification not separated
  3. 2000 High

    Placed NEUROD1 within a transcriptional cascade by showing Neurogenin3 directly activates its promoter through E-boxes, defining upstream regulatory logic of endocrine differentiation.

    Evidence Promoter deletion/mutagenesis, EMSA, reporter assays, and Xenopus ectopic expression

    PMID:10639171 PMID:10757813

    Open questions at the time
    • Did not establish whether the cascade operates identically across all endocrine and neural lineages
  4. 2002 Medium

    Resolved how NEUROD1 selects targets and is itself modulated, identifying direct activation of SUR1, dual activator/repressor function, c-Myc competition, MAPK-driven nuclear shuttling via Ser274, Id2 antagonism, and Finb/RREB-1 cooperation.

    Evidence EMSA, reporter assays with E-box mutants, dominant-negatives, subcellular fractionation, MEK inhibition, and Co-IP across multiple cell lines

    PMID:11799123 PMID:11861467 PMID:11981044 PMID:12297313 PMID:12482979 PMID:12526101

    Open questions at the time
    • Most regulatory interactions characterized in single labs on episomal reporters
    • Physiological weighting of each input in vivo unclear
  5. 2004 High

    Connected NEUROD1 to activity-dependent signaling and chromatin remodeling, showing CaMKII phosphorylation at Ser336 stimulates its activity to drive dendritogenesis and that Brg1/SWI-SNF is required for its transactivation.

    Evidence In vitro kinase assay with site-directed mutagenesis, neuronal knockdown with dendritic morphometry, Co-IP with dominant-negative Brg1 and reporter assays

    PMID:14741104 PMID:15576411

    Open questions at the time
    • Did not map genome-wide chromatin remodeling events
    • Did not resolve how phosphorylation alters DNA binding or cofactor recruitment
  6. 2005 Medium

    Linked NEUROD1 expression to metabolic and stress signaling and explored protein-level entry, defining a FoxO1-PML-Sirt1 axis controlling its expression and a heparan-sulfate-dependent transduction route.

    Evidence Co-IP of FoxO1-PML-Sirt1 complex with acetylation mutants and transgenic mice; protein transduction with subcellular imaging and insulin promoter binding

    PMID:15906379 PMID:16154098 PMID:16186386

    Open questions at the time
    • Protein transduction route characterized in single lab without independent confirmation
    • Physiological relevance of extracellular NEUROD1 entry unclear
  7. 2007 High

    Provided structural and genomic logic for NEUROD1 DNA recognition, determining the E47-NEUROD1 heterodimer crystal structure on the insulin E-box and mapping neuron-specific target enhancers and cooperating factors.

    Evidence X-ray crystallography of bHLH heterodimer, ChIP and enhancer reporter assays in Xenopus and mouse, C/EBP Co-IP and ChIP

    PMID:17149999 PMID:17254333 PMID:18007592 PMID:18069799

    Open questions at the time
    • Structure limited to bHLH domain on one E-box
    • Did not define how heterodimer choice is regulated in vivo
  8. 2010 High

    Defined NEUROD1's role in functional cell maturation and circuit-level outcomes, showing it is required for glucose-responsive beta-cell maturation, spiral/vestibular neuron survival and axon guidance, hair-cell fate suppression, and opioid-regulated spine stability.

    Evidence Conditional knockouts with glucose/insulin assays and metabolic profiling; ear conditional knockouts with anatomical tracing; CaMKII/miR-190 manipulation with spine morphometry

    PMID:18199774 PMID:20374962 PMID:20512592 PMID:20554861 PMID:20661473

    Open questions at the time
    • Direct target genes mediating each maturation/survival phenotype only partially defined
    • Tissue-specific cofactor requirements not fully resolved
  9. 2015 High

    Established NEUROD1 as a pioneer factor that reprograms silenced chromatin to euchromatin with epigenetic memory, and defined a combinatorial Insm1/Neurod1/Foxa2 module governing beta-cell maturity.

    Evidence ChIP-seq, ATAC-seq, RNA-seq with conditional induction in progenitors; Co-IP and ChIP-seq co-occupancy with conditional Insm1 ablation; zebrafish Notch epistasis

    PMID:25828096 PMID:26516211 PMID:26580854

    Open questions at the time
    • Molecular basis of pioneer access to closed chromatin not fully resolved
    • Chromatin remodeling cofactors recruited to silenced loci not exhaustively defined
  10. 2016 High

    Defined NEUROD1's oncogenic transcriptional program in neuroendocrine cancer, showing it occupies distinct loci from ASCL1, targets MYC, and promotes SCLC malignant behavior, TrkB/NCAM signaling, and G6PD-driven metabolism.

    Evidence ChIP-seq comparison with ASCL1, CRISPR/siRNA knockdown, SCLC mouse and xenograft models, metabolic flux analysis

    PMID:23553831 PMID:27452466 PMID:34657129

    Open questions at the time
    • Did not establish whether oncogenic targets overlap developmental targets
    • Mechanism of NEUROD1-vs-ASCL1 subtype divergence unclear
  11. 2017 Medium

    Revealed a non-canonical role as a DNA-binding-dependent coactivator conferring nuclear receptor selectivity, with NeuroD factors marking mineralocorticoid- but not glucocorticoid-receptor binding sites.

    Evidence MR/GR ChIP-seq, de novo motif and co-occupancy analysis, reporter assays in HEK293

    PMID:28324065

    Open questions at the time
    • Physiological consequence of MR coactivation in vivo not established
    • Whether NEUROD1 itself (versus NeuroD2) mediates this in target tissues unclear
  12. 2019 Medium

    Extended the pioneer-factor model to cell reprogramming and tumor differentiation, showing NEUROD1 occupies bivalent chromatin in microglia and that its epigenetic repression in medulloblastoma can be relieved to force differentiation.

    Evidence ChIP-seq for H3K4me3/H3K27me3, ATAC-seq, lentiviral expression; scRNA-seq with EZH2 inhibition and H3K27me3 ChIP

    PMID:30638745 PMID:32579914

    Open questions at the time
    • Microglia-to-neuron conversion claim later contested
    • Direct versus indirect chromatin effects not fully separated
  13. 2021 High

    Refined developmental and reprogramming roles, demonstrating NEUROD1 requirement for human and mouse endocrine differentiation and perinatal islet proliferation, while lineage tracing refuted prior microglia-to-neuron conversion as artifactual.

    Evidence NEUROD1 inactivation in human ESCs and mouse conditional knockouts with transcriptome/H3K27me3 profiling; strict Cre-lox lineage tracing with cell-death assays

    PMID:31519700 PMID:34201511 PMID:34875233

    Open questions at the time
    • Reconciliation of pioneer activity with failure to reprogram microglia not mechanistically resolved
    • Boundaries of NEUROD1 reprogramming competence across cell types undefined
  14. 2023 High

    Consolidated NEUROD1 as a maintainer of a permissive endocrine chromatin landscape and a cooperating driver of cortical migration with Tcf12, linking its pioneer activity to lineage stability and morphogenesis.

    Evidence Conditional knockout with transcriptome and H3K27me3 ChIP-seq/ATAC-seq; Co-IP and co-occupancy ChIP-seq with in vivo cortical migration assays; BET protein Co-IP, ChIP-seq, xenograft

    PMID:35147187 PMID:36378541 PMID:37689751

    Open questions at the time
    • How NEUROD1 partner choice (Tcf12, Insm1/Foxa2, BET, E47) is determined in each tissue remains unresolved
    • Direct chromatin-modifying enzymes recruited by NEUROD1 not fully identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NEUROD1 selects its pioneer target loci, recruits chromatin remodelers, and switches between distinct cofactor partnerships across neural, endocrine, and oncogenic contexts remains unresolved.
  • No structural model of NEUROD1 engaging nucleosomal/closed chromatin
  • Mechanism coupling post-translational modification to target selection unknown
  • Determinants of tissue-specific partner choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-4839726 Chromatin organization 3
Partners
BRD4CEBPAFOXA2INSM1RREB1SMARCA4 (BRG1)TCF12TCF3 (E47)
Complex memberships
E47-NEUROD1 bHLH heterodimerINSM1-cyclin D1-HDAC1/3 repressor complex (at NeuroD1 promoter)Insm1-Neurod1-Foxa2 complex

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 NeuroD (NEUROD1) is a bHLH transcription factor that, when ectopically expressed in Xenopus embryos, converts presumptive epidermal cells into fully differentiated neurons and causes premature differentiation of neuronal precursors, demonstrating it acts as a neuronal differentiation/determination factor capable of bypassing normal inhibitory signals. Ectopic expression in Xenopus embryos (gain-of-function), morphological and molecular phenotypic readout Science High 7754368
1997 BETA2/NeuroD (NEUROD1) is required for normal pancreatic islet morphogenesis and terminal differentiation of insulin-producing beta cells; knockout mice develop severe diabetes with striking reduction in beta cell number and failure to form mature islets, and also fail to develop secretin- and cholecystokinin-producing enteroendocrine cells. Gene targeting / knockout mice, histology, immunocytochemistry Genes & development High 9308961
1997 NeuroD1/beta2 is expressed in corticotroph cells of the pituitary and forms heterodimeric complexes (CUTE complexes) with ubiquitous bHLH dimerization partners that specifically bind and activate transcription from the POMC promoter E-box; NeuroD1 heterodimers activate transcription in synergy with the homeodomain protein Ptx1. Co-immunoprecipitation, EMSA, reporter gene transactivation assays, in situ hybridization Molecular and cellular biology High 9343431
1999 NeuroD plays multiple roles in developing rodent retina: it acts as a critical regulator of neuron versus glial cell fate (NeuroD-null retinas show 3-4 fold increase in Müller glia), promotes amacrine over bipolar interneuron differentiation, and is essential for survival of a subset of rod photoreceptors. Loss-of-function (NeuroD-null mice retinal explants), gain-of-function (retroviral forced expression in rat), cell counting and marker analysis Development High 9834183
2000 BETA2/NeuroD is required for proliferation of dentate granule cell precursors after migration and for their differentiation; loss of BETA2/NeuroD results in failure to develop a dentate gyrus granule cell layer and causes spontaneous limbic seizures. BETA2/NeuroD null mice, immunocytochemistry, electrophysiology PNAS High 10639171
2000 Neurogenin 3 (ngn3) acts upstream of BETA2/NeuroD and directly activates the BETA2 promoter through two proximal E-box sequences (E1 and E3) by binding as an ngn3-E47 heterodimer, placing BETA2/NeuroD downstream of ngn3 in the pancreatic endocrine differentiation cascade. Ectopic expression in Xenopus, promoter deletion/mutation analysis, EMSA, reporter gene assays in endocrine cell lines Molecular and cellular biology High 10757813
2002 Math3 and NeuroD are functionally redundant for amacrine cell fate specification in the retina; in Math3-NeuroD double-mutant retina, amacrine cells are completely absent and cells that would become amacrine cells adopt ganglion and glial fates instead. Co-expression of Math3 or NeuroD with homeodomain proteins Pax6 or Six3 is required to specify amacrine cell fate. Double-knockout mice, retinal explant cultures, misexpression experiments Development High 11861467
2004 CaMKII phosphorylates NeuroD at distinct sites including Ser336 in primary neurons, and this phosphorylation stimulates NeuroD transcriptional activity and dendritic growth; genetic knockdown of NeuroD in cerebellar granule neurons impairs dendritic generation and maintenance while sparing axonal development, defining a CaMKII-NeuroD signaling pathway for activity-dependent dendritogenesis. Genetic knockdown in primary neurons and organotypic cerebellar slices, in vitro kinase assay, site-directed mutagenesis, dendritic morphometry Neuron High 14741104
2004 The SWI/SNF catalytic subunit Brg1 physically associates with NeuroD and is essential for NeuroD-mediated transactivation; loss of Brg1 function abolishes the ability of NeuroD to drive neuronal differentiation in Xenopus and mammalian P19 cells. Co-immunoprecipitation (Brg1-NeuroD physical interaction), dominant-negative Brg1, reporter gene transactivation assays, gain/loss-of-function in Xenopus and P19 cells Development High 15576411
2005 FoxO1 forms a complex with PML and Sirt1 to activate NeuroD (and MafA) expression, protecting beta cells against oxidative stress; acetylation of FoxO1 targets it to PML and prevents its ubiquitin-dependent degradation, linking glucose/growth factor signaling to NeuroD expression. Co-immunoprecipitation (FoxO1-Pml-Sirt1 complex), acetylation-defective and acetylation-mimicking mutants, transgenic mouse model, reporter assays Cell metabolism High 16154098
2005 BETA2/NeuroD protein contains an arginine- and lysine-rich protein transduction domain (PTD) that allows it to permeate cells via macropinocytosis; once internalized it is released from endosomes to the cytoplasm and nucleus, where it binds the insulin promoter and activates insulin gene expression. Protein transduction experiments, subcellular fractionation/imaging, insulin promoter binding assay, dose-response analysis Diabetes Medium 16186386
2005 NeuroD1 acts as both a transcriptional activator (of insulin and IAPP) and a transcriptional repressor (of somatostatin) in the same cell; ectopic NeuroD1 in a delta-cell line represses somatostatin and induces beta-cell genes including Nkx2.2, demonstrating dual activator/repressor function. Ectopic expression in pancreatic delta-cell line (TRM-6/PDX-1), reporter gene assays with insulin and somatostatin promoters, immunostaining Developmental dynamics Medium 15906379
2006 INSM1 binds to the neuroD/beta2 promoter and represses its transcription by recruiting cyclin D1 and histone deacetylases HDAC-1 and HDAC-3; cyclin D1 mediates the interaction between INSM1 and HDACs, and overexpression of cyclin D1 plus HDAC-3 enhances INSM1-mediated repression. Yeast two-hybrid, in vitro and in vivo pull-down assays, co-immunoprecipitation, ChIP, reporter gene transactivation assays Biochemical journal High 16569215
2007 Crystal structure of the E47-NeuroD1 bHLH domain heterodimer in complex with the insulin promoter E-box (CATCTG) was determined; E47 and NeuroD1 interactions in the heterodimer are comparable to E47 homodimer interactions, suggesting NeuroD1 homodimer instability drives heterodimer preference. NeuroD1 neurogenic-specific residue His115 makes an additional phosphate backbone contact that orients the heterodimer uniquely on the E-box. X-ray crystallography, protein purification, structural analysis Biochemistry High 18069799
2007 NeuroD and Neurogenin bind distinct consensus E-box sequences and regulate largely overlapping yet distinct sets of neuronal differentiation genes; they act through enhancers containing clustered, conserved consensus-binding sites to activate transcription factors, signal transducers, and cytoskeletal regulators for neuronal differentiation and migration. Target gene identification by expression profiling in Xenopus and mouse, ChIP, enhancer reporter assays in Xenopus, computational motif analysis The EMBO journal Medium 18007592
2007 C/EBPalpha/beta and NeuroD form complexes in vitro and in vivo and are co-recruited to the promoters of immediate-early genes Fos, Egr1, and Egr2 in response to BDNF/TrkB signaling; C/EBPalpha and NeuroD cooperatively activate the Fos promoter via a combined C/EBP-Ebox element. Co-immunoprecipitation (in vitro and in vivo), ChIP, reporter gene transactivation, genetic depletion of Trk receptors Neural development Medium 17254333
2002 BETA2/NeuroD activates the mouse sulfonylurea receptor 1 (SUR1) gene through a specific E-box element (E3 at -141) in cooperation with E47; a dominant-negative BETA2/NeuroD represses SUR1 promoter activity, and mutation of E3 eliminates BETA2/NeuroD stimulation, establishing direct transcriptional regulation of SUR1 by BETA2/NeuroD. Reporter gene assays, EMSA, dominant-negative constructs, promoter deletion/mutation analysis Molecular endocrinology Medium 11981044
2002 c-Myc suppresses insulin gene transcription by competing with NeuroD/BETA2 for binding to the E-box element in the insulin promoter; c-Myc does not activate insulin gene expression and lacks a coactivator interaction with p300 (which is a NeuroD coactivator), providing the mechanism for c-Myc-mediated inhibition of NeuroD function. Gel-shift (EMSA), reporter gene assays with E-box mutant promoters, co-expression in multiple cell lines including primary islets, adenoviral overexpression Journal of Biological Chemistry Medium 11799123
2002 BETA2/NeuroD activates transcription of the secretin gene through E-box binding; the zinc finger protein Finb/RREB-1 physically associates with BETA2 and potentiates its transcriptional activation of the secretin gene by DNA binding to an adjacent cis-element, requiring both DNA binding and physical interaction with BETA2. Expression cloning, co-immunoprecipitation, reporter gene assays, promoter mutation analysis Molecular and cellular biology Medium 12482979
2002 Id2 inhibits BETA2/NeuroD function by interacting with E47 (the bHLH dimerization partner) and blocking BETA2/NeuroD binding to its E-box target sequence, thereby inhibiting E-box-mediated gene expression in a dose-dependent manner. Yeast two-hybrid, EMSA, reporter gene assays, co-expression in HIT and HeLa cells Experimental & molecular medicine Medium 12526101
2002 Glucose stimulation of the MEK-ERK (MAPK) signaling pathway promotes NeuroD1 nuclear localization in MIN6 beta-cells; at low glucose NeuroD1 is predominantly cytoplasmic, and at high glucose it translocates to the nucleus. Mutation of the MAPK phosphorylation site S274A or MEK inhibition increases cytoplasmic NeuroD1 at high glucose and attenuates NeuroD1-mediated transcription. Subcellular fractionation/immunofluorescence, MEK inhibitor (PD98059), site-directed mutagenesis (S274A), reporter gene assay FEBS letters Medium 12297313
2003 Huntingtin (Htt) interacts with NeuroD (ND) indirectly via huntingtin-associated protein 1 (HAP1), and mixed-lineage kinase 2 (MLK2) phosphorylates and stimulates NeuroD activity; Htt and HAP1 facilitate MLK2-mediated activation of NeuroD, identifying NeuroD as the first neuron-specific transcription factor whose activity is modulated by Htt. Yeast two-hybrid screen, co-immunoprecipitation, kinase assay, reporter gene transactivation assays PNAS Medium 12881483
2007 Cell surface heparan sulfate proteoglycans are required for BETA2/NeuroD protein internalization; soluble heparin and heparinase III treatment impair NeuroD entry, while chondroitin sulfate and chondroitinase are ineffective; mutant CHO cell lines deficient in GAG biosynthesis confirm that selective sulfation of heparan sulfate is important for NeuroD-heparan sulfate recognition. Competitive inhibition with soluble GAGs, enzymatic treatment (heparinase III, chondroitinase), GAG-biosynthesis-deficient CHO mutant cell lines Human gene therapy Medium 17149999
2008 NeuroD1 is required for sustained expression of thyroid hormone receptor beta2 (TRbeta2) in immature cone photoreceptors; NeuroD1-deficient mice display an opsin phenotype identical to TRbeta2-deficient mice (uniform S-opsin, loss of M-opsin), and NeuroD1 directly binds an E-box in the TRbeta2 intron control region. Reintroduction of NeuroD1 into NeuroD1-null retinal explants restores TRbeta2 expression. NeuroD1 knockout mice, ChIP (E-box binding), retinal explant rescue experiment, opsin immunostaining Journal of Neuroscience High 18199774
2010 NeuroD activity is regulated downstream of mu-opioid receptor agonists via CaMKIIalpha-dependent phosphorylation: morphine reduces CaMKIIalpha activity and thus net NeuroD activity, while fentanyl maintains NeuroD activity by also increasing NeuroD protein level through suppression of miR-190. Decreased NeuroD activity leads to reduced dendritic spine stability, which can be rescued by NeuroD overexpression. CaMKII activity assays, miR-190 overexpression, KN93 inhibitor, NeuroD overexpression rescue, dendritic spine morphometry, downstream target gene mRNA measurement Journal of Neuroscience Medium 20554861
2010 NeuroD is required for beta cell maturation and functional glucose responsiveness; conditional deletion of neuroD in insulin-expressing cells results in severe glucose intolerance, poor glucose-stimulated insulin secretion, a metabolic profile resembling immature beta cells (elevated glycolytic genes, LDHA, elevated basal insulin secretion), defective K(ATP) channel-mediated insulin secretion, and near-complete loss of ins1 expression. Conditional knockout mice (insulin-Cre), glucose tolerance tests, insulin secretion assays, gene expression analysis, metabolic profiling Cell metabolism High 20374962
2010 Neurod1 is essential for survival of most spiral and vestibular neurons; conditional deletion in the ear results in vestibular and cochlear afferents projecting centrally as a single mixed nerve (rather than segregated), disorganized peripheral innervation with collaterals to multiple endorgans, and loss of tonotopic organization. Conditional knockout (Pax2-Cre), anatomical tracing, immunofluorescence, comparison with systemic null mice Cell and tissue research High 20512592
2010 Neurod1 suppresses hair cell differentiation in inner ear sensory ganglia; conditional deletion of Neurod1 in the ear results in Atoh1 expression and hair cell differentiation within the ganglion. Neurod1 also regulates hair cell subtype differentiation in the cochlea, with conditional null mice showing premature gene expression changes in the cochlear apex and transformation of outer hair cells into inner hair cells. Conditional knockout (Pax2-Cre), immunofluorescence, in situ hybridization, gene expression analysis PLoS One High 20661473
2013 NeuroD1 promotes survival and migration in neuroendocrine lung carcinomas by regulating expression of the receptor tyrosine kinase TrkB and the prometastatic signaling molecule NCAM as downstream target genes. NeuroD1 knockdown/loss-of-function in SCLC cell lines, gene expression analysis, functional migration and survival assays PNAS Medium 23553831
2015 NeuroD1 acts as a pioneer transcription factor that directly binds epigenetically silenced regulatory elements of neuronal genes, reprogramming heterochromatin to euchromatin and remodeling the transcription factor landscape to establish transcriptional competence; NeuroD1 also induces epithelial-to-mesenchymal transition genes to promote neuronal migration. These epigenetic changes are maintained beyond the transient NeuroD1 induction (epigenetic memory). ChIP-seq, ATAC-seq, RNA-seq, chromatin accessibility assays, conditional NeuroD1 induction system in neural progenitors The EMBO journal High 26516211
2015 Insm1, Neurod1, and Foxa2 directly interact with each other and together co-occupy regulatory sequences in the genome of mature pancreatic beta-cells; combinatorial binding of Insm1/Neurod1/Foxa2 (not Insm1 alone) explains a significant fraction of gene expression changes controlling beta-cell maturity. Co-immunoprecipitation (direct interaction of Insm1, Neurod1, Foxa2), ChIP-seq (co-occupancy), conditional Insm1 ablation in adult beta-cells, gene expression analysis The EMBO journal High 25828096
2016 NEUROD1 binds distinct genomic loci from ASCL1 in SCLC cells, regulates a mostly distinct set of genes, and targets the oncogene MYC; NEUROD1 is not required for mouse SCLC tumor formation (unlike ASCL1) but promotes malignant survival behavior in human SCLC cell lines. ChIP-seq (NEUROD1 vs ASCL1 genomic binding), gene expression analysis, CRISPR/siRNA knockdown, SCLC mouse models Cell Reports High 27452466
2017 NeuroD factors (Neurod1, Neurod2, Neurod6) act as DNA-binding-dependent coactivators for the mineralocorticoid receptor (MR) but not glucocorticoid receptor (GR) in the hippocampus by binding an Atoh/NeuroD consensus sequence adjacent to MR-specific GREs; Neurod2 is detected at hippocampal MR binding sites but not GR-exclusive sites, providing a mechanism for MR vs GR DNA-binding selectivity. ChIP-seq (MR, GR), de novo motif analysis, co-occupancy analysis, reporter gene assays in HEK293 cells Endocrinology Medium 28324065
2019 NeuroD1 functions as a pioneer transcription factor in microglia-to-neuron reprogramming by initially occupying closed chromatin regions marked by bivalent H3K4me3/H3K27me3 in microglia; these regions are subsequently resolved to monovalent H3K4me3 as neuronal identity is established. NeuroD1 also induces transcriptional repressors Scrt1 and Meis2 to decrease microglial gene expression, while erasing the microglial epigenetic signature. ChIP-seq (H3K4me3, H3K27me3), ATAC-seq, RNA-seq, lentiviral NeuroD1 expression in microglia in vitro and in vivo Neuron High 30638745
2021 NeuroD1 expression induces apoptosis in microglia rather than converting them to neurons; lineage tracing revealed non-specific leakage of lentiviruses previously used in microglia-to-neuron conversion experiments, indicating that prior reports of NeuroD1-mediated microglia-to-neuron cross-lineage reprogramming were artifactual. Lineage tracing with strict Cre-lox reporter, live imaging, conditional NeuroD1 expression in microglia, cell death assays Neuron Medium 34875233
2021 NEUROD1 is required for early alpha and beta endocrine cell differentiation during mouse pancreas development; Neurod1 inactivation impairs expression of key transcription factors for alpha- and beta-cell differentiation, beta-cell proliferation, and insulin production, altering H3K27me3 histone modification patterns in promoter regions of differentially expressed genes. Conditional knockout mice, transcriptome analysis, chromatin landscape (H3K27me3 ChIP), immunofluorescence International Journal of Molecular Sciences High 34201511
2022 NeuroD1 cooperates with Tcf12 to drive neuronal migration during cortical development; Tcf12 forms a physical complex with NeuroD1, co-occupies a subset of NeuroD1 target loci, and their cooperation activates chromatin and target genes required for cell migration. In vivo manipulation demonstrates Tcf12 is essential for correct migration of newborn neurons and cortical lamination. Co-immunoprecipitation (Tcf12-NeuroD1 complex), ChIP-seq (co-occupancy), ATAC-seq, conditional in vivo manipulation, cortical migration assays Development High 35147187
2023 NEUROD1 reinforces endocrine lineage commitment and differentiation in the developing pancreas by maintaining a chromatin landscape permissive for endocrine gene expression; Neurod1 inactivation triggers downregulation of endocrine differentiation transcription factors and upregulation of non-endocrine genes, altering H3K27me3 modification patterns in promoter regions of affected genes. Conditional knockout, transcriptome sequencing, chromatin landscape analysis (H3K27me3 ChIP-seq), ATAC-seq Nature Communications High 37689751
2023 BET proteins (BRD2/3/4) physically interact with NEUROD1 and function as its transcriptional coactivators in SCLC; NEUROD1 plays a critical role in defining BET protein genomic occupancy landscapes in SCLC, and BET inhibition broadly suppresses NEUROD1-target genes (especially superenhancer-associated), inhibiting SCLC growth in vitro and in vivo. Co-immunoprecipitation (NEUROD1-BET interaction), CRISPR knockout, ChIP-seq, SCLC xenograft in vivo experiments Molecular cancer research High 36378541
2021 NeuroD1 directly binds the G6PD promoter to activate G6PD transcription, stimulating the pentose phosphate pathway in colorectal cancer cells to enhance nucleotide and NADPH production, reduce ROS, and promote DNA/lipid biosynthesis and tumor cell proliferation. ChIP (NeuroD1 binding to G6PD promoter), reporter gene assays, metabolic flux analysis, knockdown/overexpression with proliferation and tumorigenic readouts Oncogene Medium 34657129
2015 In zebrafish, NeuroD governs photoreceptor genesis via non-cell-autonomous mechanisms and functions through Notch signaling: NeuroD knockdown increases Notch pathway gene expression, and Notch inhibition rescues the cell cycle exit defect (but not photoreceptor maturation) caused by NeuroD knockdown. During adult photoreceptor regeneration, NeuroD knockdown prevents cell cycle exit and regeneration, and Notch inhibition rescues this phenotype. Genetic mosaic analysis, morpholino knockdown, CRISPR/Cas9 mutation, pharmacologic Notch inhibition, transgenic Notch activation, in situ hybridization, qRT-PCR Investigative ophthalmology & visual science High 26580854
2019 NEUROD1 is required for differentiation of human embryonic stem cells (HESCs) into insulin-expressing beta cells; inactivation of NEUROD1 in HESCs severely impairs differentiation from pancreatic progenitors and prevents full activation of the beta-cell transcription factor network. In mice, Neurod1 is required for perinatal proliferation of alpha- and beta-cells. NEUROD1 inactivation in HESCs, mouse conditional knockout, flow cytometry, gene expression analysis Diabetes High 31519700
2020 NeuroD1 expression promotes differentiation of medulloblastoma (MB) cells by activating a differentiation program; NeuroD1 expression in MB cells is epigenetically repressed by H3K27me3, and EZH2 inhibition reduces H3K27me3 at the NeuroD1 locus, increasing NeuroD1 expression, promoting MB cell differentiation, and reducing tumor growth. Single-cell RNA sequencing, NeuroD1 forced expression, EZH2 inhibitor treatment, ChIP (H3K27me3 at NeuroD1 locus), tumor growth assays Cell Reports Medium 32579914

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Conversion of Xenopus ectoderm into neurons by NeuroD, a basic helix-loop-helix protein. Science (New York, N.Y.) 931 7754368
1997 Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrine differentiation in BETA2/neuroD-deficient mice. Genes & development 820 9308961
2005 FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell metabolism 496 16154098
2020 SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 431 33011388
2016 ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs. Cell reports 419 27452466
2003 NeuroD-betacellulin gene therapy induces islet neogenesis in the liver and reverses diabetes in mice. Nature medicine 347 12704384
1999 NeuroD regulates multiple functions in the developing neural retina in rodent. Development (Cambridge, England) 305 9834183
2000 Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proceedings of the National Academy of Sciences of the United States of America 247 10639171
2000 Regulation of the pancreatic islet-specific gene BETA2 (neuroD) by neurogenin 3. Molecular and cellular biology 240 10757813
2002 Math3 and NeuroD regulate amacrine cell fate specification in the retina. Development (Cambridge, England) 222 11861467
2015 NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program. The EMBO journal 212 26516211
2010 Pancreatic beta cells require NeuroD to achieve and maintain functional maturity. Cell metabolism 212 20374962
2004 A CaMKII-NeuroD signaling pathway specifies dendritic morphogenesis. Neuron 209 14741104
1997 NeuroD1/beta2 contributes to cell-specific transcription of the proopiomelanocortin gene. Molecular and cellular biology 184 9343431
2019 Pioneer Factor NeuroD1 Rearranges Transcriptional and Epigenetic Profiles to Execute Microglia-Neuron Conversion. Neuron 176 30638745
2007 Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers. The EMBO journal 165 18007592
2004 The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Development (Cambridge, England) 164 15576411
1996 NeuroD2 and neuroD3: distinct expression patterns and transcriptional activation potentials within the neuroD gene family. Molecular and cellular biology 145 8816493
1998 Neuronal basic helix-loop-helix proteins (NEX, neuroD, NDRF): spatiotemporal expression and targeted disruption of the NEX gene in transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 9454850
2010 Neurod1 suppresses hair cell differentiation in ear ganglia and regulates hair cell subtype development in the cochlea. PloS one 101 20661473
2004 NeuroD: the predicted and the surprising. Molecules and cells 98 15650322
2005 BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence. Diabetes 97 16186386
2000 The C. elegans NeuroD homolog cnd-1 functions in multiple aspects of motor neuron fate specification. Development (Cambridge, England) 91 10976055
2013 NeuroD1 regulates survival and migration of neuroendocrine lung carcinomas via signaling molecules TrkB and NCAM. Proceedings of the National Academy of Sciences of the United States of America 88 23553831
1998 neuroD induces photoreceptor cell overproduction in vivo and de novo generation in vitro. Journal of neurobiology 86 9740021
2000 Expression of neuroD/BETA2 in mitotic and postmitotic neuronal cells during the development of nervous system. Developmental dynamics : an official publication of the American Association of Anatomists 85 10767080
2004 GATA3 and NeuroD distinguish auditory and vestibular neurons during development of the mammalian inner ear. Mechanisms of development 81 15003631
2010 Neurod1 regulates survival and formation of connections in mouse ear and brain. Cell and tissue research 80 20512592
2009 mu-Opioid receptor agonists differentially regulate the expression of miR-190 and NeuroD. Molecular pharmacology 80 19854889
2007 Crystal structure of E47-NeuroD1/beta2 bHLH domain-DNA complex: heterodimer selectivity and DNA recognition. Biochemistry 80 18069799
2021 NeuroD1 induces microglial apoptosis and cannot induce microglia-to-neuron cross-lineage reprogramming. Neuron 79 34875233
2015 Insm1 cooperates with Neurod1 and Foxa2 to maintain mature pancreatic β-cell function. The EMBO journal 79 25828096
2011 NeuroD factors regulate cell fate and neurite stratification in the developing retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 78 21593321
2017 MiR-30a-5p ameliorates spinal cord injury-induced inflammatory responses and oxidative stress by targeting Neurod 1 through MAPK/ERK signalling. Clinical and experimental pharmacology & physiology 72 28925510
2009 Involvement of Ngn2, Tbr and NeuroD proteins during postnatal olfactory bulb neurogenesis. The European journal of neuroscience 69 19200230
2008 NeuroD1 regulates expression of thyroid hormone receptor 2 and cone opsins in the developing mouse retina. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 18199774
2007 Neurotrophin/Trk receptor signaling mediates C/EBPalpha, -beta and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription. Neural development 62 17254333
1997 NeuroD and neurogenesis. Developmental neuroscience 62 9078430
2003 Stimulation of NeuroD activity by huntingtin and huntingtin-associated proteins HAP1 and MLK2. Proceedings of the National Academy of Sciences of the United States of America 61 12881483
2002 Expression domains of neuroD (nrd) in the early postembryonic zebrafish brain. Brain research bulletin 61 11922992
2002 Neogenesis of beta-cells in adult BETA2/NeuroD-deficient mice. Molecular endocrinology (Baltimore, Md.) 60 11875114
2008 NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafish. Mechanisms of development 58 19121642
2002 Induction of c-Myc expression suppresses insulin gene transcription by inhibiting NeuroD/BETA2-mediated transcriptional activation. The Journal of biological chemistry 57 11799123
1999 Association of polymorphism in the NeuroD/BETA2 gene with type 1 diabetes in the Japanese. Diabetes 57 10334323
2005 Secondary neurogenesis in the brain of the African clawed frog, Xenopus laevis, as revealed by PCNA, Delta-1, Neurogenin-related-1, and NeuroD expression. The Journal of comparative neurology 56 16025451
2005 NeuroD1 in the endocrine pancreas: localization and dual function as an activator and repressor. Developmental dynamics : an official publication of the American Association of Anatomists 54 15906379
2020 NeuroD1 Dictates Tumor Cell Differentiation in Medulloblastoma. Cell reports 52 32579914
2010 Modulations of NeuroD activity contribute to the differential effects of morphine and fentanyl on dendritic spine stability. The Journal of neuroscience : the official journal of the Society for Neuroscience 52 20554861
2017 NeuroD Factors Discriminate Mineralocorticoid From Glucocorticoid Receptor DNA Binding in the Male Rat Brain. Endocrinology 51 28324065
2006 INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene through the recruitment of cyclin D1 and histone deacetylases. The Biochemical journal 51 16569215
1999 Olfactory neuron-specific expression of NeuroD in mouse and human nasal mucosa. Cell and tissue research 47 10639731
2010 Phylotypic expression of the bHLH genes Neurogenin2, Neurod, and Mash1 in the mouse embryonic forebrain. The Journal of comparative neurology 43 20058311
2007 Induction of pancreatic islet cell differentiation by the neurogenin-neuroD cascade. Differentiation; research in biological diversity 43 17924961
2002 Transactivation of the mouse sulfonylurea receptor I gene by BETA2/NeuroD. Molecular endocrinology (Baltimore, Md.) 42 11981044
2000 NeuroD/BETA2 gene variability and diabetes: no associations to late-onset type 2 diabetes but an A45 allele may represent a susceptibility marker for type 1 diabetes among Danes. Danish Study Group of Diabetes in Childhood, and the Danish IDDM Epidemiology and Genetics Group. Diabetes 42 10905500
2015 The bHLH Transcription Factor NeuroD Governs Photoreceptor Genesis and Regeneration Through Delta-Notch Signaling. Investigative ophthalmology & visual science 41 26580854
2003 Novel transcriptional potentiation of BETA2/NeuroD on the secretin gene promoter by the DNA-binding protein Finb/RREB-1. Molecular and cellular biology 41 12482979
2009 Combination of MafA, PDX-1 and NeuroD is a useful tool to efficiently induce insulin-producing surrogate beta-cells. Current medicinal chemistry 39 19689288
2002 Glucose induced MAPK signalling influences NeuroD1-mediated activation and nuclear localization. FEBS letters 38 12297313
2023 Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/β-catenin/NeuroD1 pathway. Molecular medicine (Cambridge, Mass.) 37 37667187
2022 Promoters of ASCL1- and NEUROD1-dependent genes are specific targets of lurbinectedin in SCLC cells. EMBO molecular medicine 37 35263037
2019 Murine Perinatal β-Cell Proliferation and the Differentiation of Human Stem Cell-Derived Insulin-Expressing Cells Require NEUROD1. Diabetes 37 31519700
2017 NEUROD1-deficient diabetes (MODY6): Identification of the first cases in Japanese and the clinical features. Pediatric diabetes 37 28664602
2007 NeuroD1: developmental expression and regulated genes in the rodent pineal gland. Journal of neurochemistry 37 17630985
2022 Transcriptomic analyses of NeuroD1-mediated astrocyte-to-neuron conversion. Developmental neurobiology 36 35606902
2008 Rosiglitazone stimulates the release and synthesis of insulin by enhancing GLUT-2, glucokinase and BETA2/NeuroD expression. Biochemical and biophysical research communications 36 18191635
1998 The role of NeuroD as a differentiation factor in the mammalian retina. Journal of molecular neuroscience : MN 36 10096043
2019 Genetic Dissection and Clinical Features of MODY6 (NEUROD1-MODY). Current diabetes reports 35 30793219
2010 Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6. Development (Cambridge, England) 35 20534668
2013 Ascl1b and Neurod1, instead of Neurog3, control pancreatic endocrine cell fate in zebrafish. BMC biology 34 23835295
2022 Tcf12 and NeuroD1 cooperatively drive neuronal migration during cortical development. Development (Cambridge, England) 33 35147187
2021 NEUROD1 Is Required for the Early α and β Endocrine Differentiation in the Pancreas. International journal of molecular sciences 32 34201511
2019 Intestinal Neurod1 expression impairs paneth cell differentiation and promotes enteroendocrine lineage specification. Scientific reports 31 31862906
1996 The NEUROD gene maps to human chromosome 2q32 and mouse chromosome 2. Genomics 31 8786144
2007 BETA2/NeuroD protein transduction requires cell surface heparan sulfate proteoglycans. Human gene therapy 29 17149999
2006 Functional redundancy of NSCL-1 and NeuroD during development of the petrosal and vestibulocochlear ganglia. The European journal of neuroscience 29 17004922
2002 Inhibition of BETA2/NeuroD by Id2. Experimental & molecular medicine 29 12526101
2020 Combined Atoh1 and Neurod1 Deletion Reveals Autonomous Growth of Auditory Nerve Fibers. Molecular neurobiology 28 32880858
2012 The combined expression of Pdx1 and MafA with either Ngn3 or NeuroD improves the differentiation efficiency of mouse embryonic stem cells into insulin-producing cells. Cell transplantation 28 22776709
2023 BET Inhibitors Target the SCLC-N Subtype of Small-Cell Lung Cancer by Blocking NEUROD1 Transactivation. Molecular cancer research : MCR 27 36378541
2008 The expression of NeuroD and mASH1 in the gastroenteropancreatic neuroendocrine tumors. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 27 18587321
2005 Cre/loxP-mediated inactivation of the bHLH transcription factor gene NeuroD/BETA2. Genesis (New York, N.Y. : 2000) 27 16028233
2001 Altered expression of HES-1, BETA2/NeuroD, and PDX-1 is involved in impaired insulin synthesis induced by glucocorticoids in HIT-T15 cells. Biochemical and biophysical research communications 27 11549279
2023 NEUROD1 reinforces endocrine cell fate acquisition in pancreatic development. Nature communications 26 37689751
2017 Rapamycin promotes differentiation increasing βIII-tubulin, NeuN, and NeuroD while suppressing nestin expression in glioblastoma cells. Oncotarget 26 28418837
2023 Overexpressing NeuroD1 reprograms Müller cells into various types of retinal neurons. Neural regeneration research 25 36255002
2012 Using the Tg(nrd:egfp)/albino zebrafish line to characterize in vivo expression of neurod. PloS one 25 22235264
2001 NeuroD/beta2 gene G-->A polymorphism may affect onset pattern of type 1 diabetes in Japanese. Diabetes care 25 11473083
2020 NeuroD1 overexpression in spinal neurons accelerates axonal regeneration after sciatic nerve injury. Experimental neurology 24 31991126
2020 NEUROD1 is highly expressed in extensive-disease small cell lung cancer and promotes tumor cell migration. Lung cancer (Amsterdam, Netherlands) 24 32526603
2021 NeuroD1 promotes tumor cell proliferation and tumorigenesis by directly activating the pentose phosphate pathway in colorectal carcinoma. Oncogene 23 34657129
2003 Expression of Hes6 and NeuroD in the olfactory epithelium, vomeronasal organ and non-sensory patches. Chemical senses 23 12714442
2015 Differential levels of Neurod establish zebrafish endocrine pancreas cell fates. Developmental biology 22 25797153
1999 Structure and regulation of the human NeuroD (BETA2/BHF1) gene. Brain research. Molecular brain research 22 10366743
1997 cDNA cloning and expression analysis of NeuroD mRNA in human retina. Biochemical and biophysical research communications 22 9144558
2023 Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma. Histopathology 21 36715573
2014 Differentiation of iPSCs into insulin-producing cells via adenoviral transfection of PDX-1, NeuroD1 and MafA. Diabetes research and clinical practice 21 24794627
2005 Inhibition of neurogenesis by SRp38, a neuroD-regulated RNA-binding protein. Development (Cambridge, England) 21 15728676
2004 Lack of association of the Ala(45)Thr polymorphism and other common variants of the NeuroD gene with type 1 diabetes. Diabetes 21 15047635
2020 Effects of Neurod1 Expression on Mouse and Human Schwannoma Cells. The Laryngoscope 20 32438526

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