Affinage

FOXD3

Forkhead box protein D3 · UniProt Q9UJU5

Length
478 aa
Mass
47.6 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FOXD3 is a forkhead-box transcription factor that maintains pluripotency and multipotency in embryonic stem cells and neural crest progenitors by dynamically remodeling enhancer chromatin. In ESCs, FOXD3 primes enhancers by recruiting the SWI/SNF ATPase BRG1 to open chromatin while simultaneously recruiting HDAC1/2 to restrain premature activation, and it decommissions naive-pluripotency enhancers during the transition to primed pluripotency (PMID:26748757, PMID:26748758). In neural crest development, FOXD3 functions downstream of Pax3/Pax7 and cooperates with Tfap2a to specify neural crest identity, activate snai1b/sox10, maintain neural versus mesenchymal potential, and repress melanocyte fate through direct transcriptional repression of mitfa (PMID:11684651, PMID:16499899, PMID:21228004, PMID:20460180). In cancer, FOXD3 is upregulated following BRAF inhibition in melanoma where it confers adaptive resistance to cell death and represses migration via Rnd3 downregulation, and it acts as a transcriptional activator of tumor-suppressive targets including NDRG1, miR-137, and miR-214 in other tumor types (PMID:21996740, PMID:21478267, PMID:24269992, PMID:27811858).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 Medium

    Identifying where FOXD3 is expressed in embryogenesis was the prerequisite for all functional studies: in situ hybridization established its presence in premigratory/migrating neural crest cells and spinal cord motor neuron progenitors.

    Evidence In situ hybridization and immunostaining in mouse embryos

    PMID:9767163

    Open questions at the time
    • Expression alone does not demonstrate function
    • No loss-of-function data at this stage
  2. 2001 High

    The central question of whether FOXD3 is necessary and sufficient for neural crest specification was resolved: gain-of-function in chick and dominant-negative in Xenopus showed FOXD3 promotes neural crest fate downstream of Pax3 and upstream of Slug, independently of RhoB.

    Evidence Chick neural tube electroporation, Xenopus dominant-negative injection with Slug rescue, Pax3 mutant epistasis

    PMID:11493569 PMID:11684651

    Open questions at the time
    • Endogenous loss-of-function in mammals not yet tested
    • Direct transcriptional targets in neural crest unknown
    • Mechanism of delamination induction unclear
  3. 2002 High

    Whether FOXD3 has roles beyond neural crest—specifically in pluripotent stem cells—was answered by the knockout mouse: Foxd3-null embryos lose epiblast cells and fail to establish ES lines, establishing FOXD3 as essential for progenitor cell maintenance.

    Evidence Foxd3 homozygous knockout mouse, chimera analysis, blastocyst outgrowth culture

    PMID:12381664

    Open questions at the time
    • Molecular targets in epiblast not identified
    • Whether self-renewal or survival is the primary defect was unclear
  4. 2006 High

    Two studies established direct transcriptional targets of FOXD3: in zebrafish neural crest, foxd3 loss (sym1 mutant) reduced snai1b and sox10 expression during specification; separately, FOXD3 was shown to bind and transactivate the myf5 promoter in somites, revealing tissue-specific target selection.

    Evidence Zebrafish sym1 mutant in situ hybridization; yeast one-hybrid and luciferase reporter for myf5 promoter; morpholino knockdown with rescue

    PMID:16386728 PMID:16499899

    Open questions at the time
    • Genome-wide target identification not yet performed
    • Whether foxd3 directly binds snai1b/sox10 regulatory regions was unknown
  5. 2007 High

    How FOXD3 controls pigment cell fate was clarified: Foxd3 directly binds and represses the mitfa promoter, and Hdac1 normally silences foxd3 to permit melanogenesis—establishing a Hdac1⊣Foxd3⊣mitfa regulatory hierarchy.

    Evidence Zebrafish hdac1 mutant analysis, foxd3 morpholino rescue of melanophore defects, Foxd3 chromatin/promoter binding at mitfa

    PMID:18068699

    Open questions at the time
    • Whether this hierarchy is conserved in mammals was untested
    • How Hdac1 silences foxd3 transcription mechanistically was unknown
  6. 2008 High

    The specific cellular defect in Foxd3-null ESCs was dissected: conditional deletion showed that self-renewal, survival, and lineage restriction all depend on Foxd3, even when Oct4/Sox2/Nanog persist, separating FOXD3 function from the core pluripotency network.

    Evidence Tamoxifen-inducible conditional Foxd3 deletion in mouse ESCs, clonal self-renewal and apoptosis assays

    PMID:18653770

    Open questions at the time
    • Direct chromatin targets in ESCs not mapped
    • Mechanism of apoptosis suppression unclear
  7. 2010 High

    Genetic epistasis with double foxd3;mitfa mutants in zebrafish demonstrated that Foxd3's promotion of iridophore fate operates by repressing mitfa—melanocyte commitment is the default that Foxd3 actively blocks.

    Evidence Zebrafish double mutant genetics with lineage tracing using photoconvertible EosFP

    PMID:20460180

    Open questions at the time
    • Positive targets promoting iridophore identity beyond pnp4a not identified
    • Mammalian relevance untested
  8. 2011 High

    Multiple studies collectively defined FOXD3's role in maintaining multipotency within the neural crest lineage: conditional deletion in mouse neural crest caused loss of neural derivatives and ectopic mesenchymal fates, compound Foxd3/Pax3 mutants revealed dose-sensitive cooperation in cardiac neural crest survival, and zebrafish double mutants with tfap2a showed complete neural crest ablation.

    Evidence Mouse conditional NC-specific Foxd3 KO with single-cell fate mapping; Foxd3/Pax3 compound mouse mutants; zebrafish foxd3/tfap2a double mutants

    PMID:21228004 PMID:21254333 PMID:21963426

    Open questions at the time
    • Direct targets maintaining neural potential vs. repressing mesenchymal fate not distinguished genome-wide
    • Signaling pathways mediating the Foxd3/Tfap2a synergy not fully resolved
  9. 2011 Medium

    FOXD3's relevance in cancer was established: BRAF inhibitor treatment upregulates FOXD3 in mutant-BRAF melanoma, conferring adaptive resistance to cell death and suppressing migration/invasion via direct transcriptional repression of Rnd3.

    Evidence siRNA knockdown and ectopic expression in melanoma cell lines treated with PLX4032/PLX4720; ChIP at Rnd3 promoter; ROCK inhibitor rescue

    PMID:21478267 PMID:21996740

    Open questions at the time
    • In vivo relevance of FOXD3-mediated resistance not demonstrated with genetic models
    • Upstream mechanism of FOXD3 induction by BRAF inhibition unknown
    • Single-lab findings for each study
  10. 2012 High

    The upstream regulation of FOXD3 itself was resolved: two distinct enhancers (NC1, NC2) drive cranial vs. vagal/trunk neural crest expression, with Pax7/Msx1/2/Ets1 directly binding NC1 and Zic1 binding NC2.

    Evidence Enhancer reporter assays in chick, in vivo ChIP, morpholino knockdowns, systematic enhancer mutagenesis

    PMID:23284303

    Open questions at the time
    • Whether these enhancers are conserved and functional in mammals not tested
    • How signaling pathways converge on these transcription factors at the enhancers is unclear
  11. 2013 Medium

    FOXD3's tumor-suppressive transcriptional activity was expanded: it directly binds the NDRG1 promoter to activate transcription in neuroblastoma, suppressing VEGF, MMP9, and metastasis, and regulates melanocyte vs. Schwann cell precursor balance in neural crest derivatives.

    Evidence ChIP and luciferase reporter at NDRG1 promoter, NDRG1 rescue in xenografts; avian gain-of-function and mouse conditional KO with lineage tracing for fate balance

    PMID:23858437 PMID:24269992

    Open questions at the time
    • NDRG1 regulation by FOXD3 shown in single lab
    • Whether FOXD3 is silenced in primary neuroblastomas by epigenetic mechanisms needs confirmation
  12. 2016 High

    The chromatin-level mechanism of FOXD3 was defined: FOXD3 simultaneously recruits BRG1 (SWI/SNF) to open chromatin and HDAC1/2 to prevent full activation, thereby priming enhancers for future expression; it also decommissions naive-pluripotency enhancers during the ESC-to-EpiSC transition and must be silenced for primordial germ cell specification.

    Evidence ChIP-seq, ATAC-seq, co-immunoprecipitation of FOXD3 with BRG1 and HDAC1/2, conditional deletion comparing ESC and EpiSC chromatin states, RNA-seq

    PMID:26748757 PMID:26748758

    Open questions at the time
    • Structural basis of FOXD3 interaction with BRG1 and HDAC1/2 unknown
    • Whether the priming mechanism operates identically in neural crest cells untested
    • Genome-wide target overlap between ESC and neural crest contexts not compared
  13. 2020 Medium

    FOXD3's immunomodulatory dimension in melanoma was uncovered: BRAF inhibition-induced FOXD3 reduces VISTA expression on melanoma cells, and melanoma-specific VISTA promotes tumor onset by expanding T regulatory cells and enhancing PD-L1 on tumor-infiltrating macrophages.

    Evidence FOXD3 overexpression/knockdown in melanoma cells, VISTA expression analysis, in vivo xenograft, flow cytometry of immune infiltrates

    PMID:31940493

    Open questions at the time
    • Whether FOXD3 directly binds VISTA regulatory elements not tested (no ChIP)
    • Single lab, in vivo model is xenograft not syngeneic/autochthonous
    • Clinical relevance of FOXD3-VISTA axis in BRAF-inhibitor-treated patients unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how FOXD3's enhancer-priming mechanism in ESCs relates to its function in neural crest and other progenitors; whether the same BRG1/HDAC1/2 co-recruitment operates in all FOXD3-dependent contexts; and what drives the context-dependent switch between FOXD3's activator and repressor activities at specific loci.
  • No genome-wide chromatin profiling of FOXD3 in neural crest cells
  • Structural basis of FOXD3-cofactor interactions unknown
  • In vivo genetic validation of FOXD3-mediated drug resistance in melanoma lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 7 GO:0042393 histone binding 1
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 9 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-4839726 Chromatin organization 2
Partners
BRG1HDAC1HDAC2PAX3PAX7TFAP2A

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Foxd3 is required for maintenance of pluripotent epiblast cells in the early mouse embryo; Foxd3-/- embryos lose epiblast cells, expand extraembryonic tissues, and cannot establish ES cell lines, demonstrating Foxd3 is essential for progenitor cell maintenance in vivo. Homozygous knockout mouse, chimera analysis, in vitro blastocyst culture, immunostaining for Oct4/Sox2/Fgf4 Genes & development High 12381664
2001 Foxd3 is expressed in premigratory and migratory neural crest cells downstream of Pax3; misexpression of Foxd3 in the chick neural tube promotes neural crest-like fate (HNK1/Cad7 upregulation, delamination, emigration) and suppresses interneuron differentiation, acting independently of Slug and RhoB. In situ hybridization, chick neural tube electroporation/misexpression, Pax3 mutant mouse analysis Development (Cambridge, England) High 11684651
2001 FoxD3 is required for neural crest determination in Xenopus; dominant-negative FoxD3 inhibits neural crest differentiation in vivo without suppressing CNS marker Sox2, and FoxD3 functions upstream of Slug in the neural crest specification pathway. Dominant-negative FoxD3 construct injection in Xenopus embryos, animal cap explant assays, marker rescue with SLUG co-injection Development (Cambridge, England) High 11493569
1998 Hfh2 (Foxd3) is expressed in premigratory and migrating neural crest cells in the early mouse embryo and in motor neuron progenitors in the developing spinal cord; the Hfh2 gene was mapped to mouse chromosome 4. In situ hybridization, immunostaining, linkage analysis Mechanisms of development Medium 9767163
2006 Zebrafish foxd3 (sym1 mutant) is required for neural crest specification, migration, and survival: sym1 mutants have normal premigratory neural crest numbers but reduced snai1b and sox10 expression, delayed migration, fewer migratory trunk neural crest cells, and aberrant apoptosis in hindbrain neural crest. Zebrafish forward genetics (sym1 nucleotide deletion), in situ hybridization for marker genes, TUNEL apoptosis assay Developmental biology High 16499899
2008 Foxd3 is required for ES cell self-renewal and survival; conditional deletion of Foxd3 in mouse ESCs causes increased apoptosis, decreased clonal self-renewal, and precocious differentiation along trophectoderm, endoderm, and mesendoderm lineages despite continued Oct4, Sox2, and Nanog expression. Conditional knockout (tamoxifen-inducible Cre), proliferation/apoptosis assays, clonal self-renewal assay, differentiation marker analysis Stem cells (Dayton, Ohio) High 18653770
2010 Foxd3 represses mitfa (MITF-a) transcription to promote iridophore development over melanophore fate in zebrafish; Foxd3 co-localizes with pnp4a in early iridoblasts and is necessary for its expression; double foxd3;mitfa mutants restore iridophore numbers lost in foxd3 single mutants. Zebrafish genetics (double mutants), in situ hybridization, cell lineage tracing with EosFP photoconvertible marker Developmental biology High 20460180
2007 Hdac1 represses foxd3 expression in neural crest cells to permit mitfa-dependent melanogenesis; in hdac1 mutants foxd3 is overexpressed, reducing mitfa+ melanoblasts; partial knockdown of foxd3 in hdac1 mutants rescues mitfa expression and melanophore defects. Additionally, Foxd3 physically interacts with the mitfa promoter. Zebrafish hdac1 mutant analysis, foxd3 morpholino knockdown rescue, chromatin/promoter interaction assay for Foxd3 at mitfa promoter Developmental biology High 18068699
2011 Foxd3 is required in neural crest stem cells to maintain neural potential and repress mesenchymal fates; conditional deletion of Foxd3 in mouse NC cells results in loss of neural derivatives, ectopic vascular smooth muscle in the aorta, precocious osteoblast/chondrocyte differentiation, and a shift from neural to myofibroblast potential at the single-cell level. Conditional NC-specific Foxd3 knockout mouse, single-cell fate mapping, immunohistochemistry, clonal culture assays Development (Cambridge, England) High 21228004
2011 Foxd3 and Pax3 genetically interact in cardiac neural crest; compound mutants (Foxd3 NC-specific homozygous deletion + Pax3 heterozygous) show fully penetrant persistent truncus arteriosus, severe thymus hypoplasia, increased cell death in neural folds, and near-complete absence of NC caudal to the first pharyngeal arch. Double mutant mouse genetics, immunohistochemistry, TUNEL assay for cell death Genesis (New York, N.Y. : 2000) High 21254333
2011 Foxd3 and Tfap2a act together in zebrafish to induce neural crest by maintaining the balance of Bmp and Wnt signaling; double mob;mos mutants completely lack all neural crest-derived tissues; foxd3 overexpression enhances tfap2a-mediated ectopic neural crest induction by overriding neural plate border limits. Zebrafish double mutant analysis, in situ hybridization, foxd3 mRNA overexpression, Bmp/Wnt pathway marker analysis Developmental biology High 21963426
2012 FoxD3 expression in the neural crest is regulated by two distinct enhancers (NC1 and NC2): NC1 drives cranial neural crest expression via Pax7, Msx1/2, and Ets1; NC2 drives vagal/trunk expression via Zic1. These transcription factors directly bind their respective enhancers. Enhancer reporter assays in chick embryos, in vivo ChIP, morpholino knockdowns, detailed mutational analysis of enhancer elements PLoS genetics High 23284303
2013 Foxd3 regulates the balance between melanocyte and Schwann cell precursor-derived melanocyte development; gain- and loss-of-function in avians and mice show Foxd3 is sufficient and necessary for this balance, and also sufficient to regulate neuronal vs. glial fate in sensory ganglia. Avian gain-of-function electroporation, conditional mouse Foxd3 knockout, lineage tracing Proceedings of the National Academy of Sciences of the United States of America High 23858437
2016 FOXD3 functions as a dual-activator/repressor of enhancers: it recruits the SWI/SNF chromatin remodeling ATPase BRG1 to promote nucleosome removal while simultaneously recruiting histone deacetylases 1/2 to inhibit maximal enhancer activation, thus priming target genes for future expression. FOXD3 switches binding sites as ESCs differentiate to epiblast cells to modulate developmental potential. ChIP-seq, ATAC-seq, co-immunoprecipitation of FOXD3 with BRG1 and HDAC1/2, conditional FOXD3 deletion, comparison of ESC and EpiSC states Cell stem cell High 26748757
2016 Foxd3 is required for exit from naive pluripotency; it acts as a repressor that decommissions active enhancers associated with naive pluripotency and early germline genes during the ESC-to-EpiSC transition, and Foxd3 must subsequently be silenced in primed pluripotent cells to allow PGC specification. Conditional Foxd3 deletion, ChIP-seq for H3K27ac and H3K4me1, RNA-seq, reporter assays Cell stem cell High 26748758
2013 FOXD3 directly binds the NDRG1 promoter and activates its transcription in neuroblastoma cells, thereby suppressing VEGF and MMP9 expression and inhibiting tumor growth, invasion, metastasis, and angiogenesis. Luciferase reporter assay, ChIP assay, FOXD3 overexpression/knockdown in NB cell lines, xenograft in vivo studies, rescue experiments with NDRG1 Oncotarget Medium 24269992
2011 FOXD3 upregulation following B-RAF/MEK inhibition (PLX4032/PLX4720) in mutant B-RAF melanoma cells confers resistance to cell death; siRNA knockdown of FOXD3 significantly enhances cell death after PLX4032/4720 treatment, and ectopic FOXD3 expression in non-adherent cells reduces cell death. siRNA knockdown, ectopic overexpression, PLX4032/PLX4720 drug treatment, cell death assays, non-adherent culture conditions Oncogene Medium 21996740
2011 FOXD3 inhibits migration, invasion, and spheroid outgrowth of mutant B-RAF melanoma cells; FOXD3 is recruited to the Rnd3 promoter and downregulates Rnd3 mRNA and protein, and inhibition of ROCK (downstream of RhoA, which is inhibited by Rnd3) partially restores migration in FOXD3-expressing cells. Ectopic FOXD3 expression, migration/invasion assays, ChIP at Rnd3 promoter, qRT-PCR, western blot, ROCK inhibitor rescue Molecular cancer research : MCR Medium 21478267
2006 Foxd3 directly binds the -82/-62 cassette of the myf5 promoter (identified by yeast one-hybrid) and transactivates myf5 expression; foxd3 morpholino knockdown downregulates myf5 in somites and adaxial cells (but not presomitic mesoderm), and is genetically downstream of pax3 in regulating myf5. Yeast one-hybrid assay, dual-luciferase reporter assay, morpholino knockdown in zebrafish, rescue with foxd3 mRNA Developmental biology Medium 16386728
2014 FoxD3 directly binds the promoter of miR-137 and activates its transcription in hepatocellular carcinoma cells; miR-137 targets AKT2 to inhibit the AKT2/mTOR pathway; FoxD3-regulated miR-137 suppresses HCC growth and metastasis in vivo. Luciferase reporter assay, ChIP for FOXD3 at miR-137 promoter, miR-137 overexpression/inhibition, AKT2 rescue experiments, xenograft studies Oncotarget Medium 24970808
2015 PAX3 and FOXD3 cooperatively promote CXCR4 expression in melanoma through a conserved intronic enhancer element; inhibition of both factors reduces melanoma cell growth, migration, and motility; these effects are rescued by CXCR4 overexpression, defining a PAX3/FOXD3→CXCR4 regulatory axis. Transcription factor knockdown/overexpression, reporter assay with intronic CXCR4 enhancer, migration/motility/growth assays, CXCR4 rescue experiments The Journal of biological chemistry Medium 26205821
2016 FOXD3 directly binds the miR-214 promoter (validated by ChIP assay) and acts as a transcription factor to activate miR-214 expression; miR-214 then targets MED19 to suppress colorectal cancer proliferation, invasion, and metastasis. ChIP assay for FOXD3 at miR-214 promoter, dual-luciferase reporter assay, bisulphite sequencing, in vitro and in vivo functional assays British journal of cancer Medium 27811858
2011 Loss of Foxd3 specifically in pancreatic beta-cells results in impaired glucose tolerance, decreased beta-cell mass, decreased beta-cell proliferation, and decreased beta-cell size during pregnancy; genes regulating proliferation (Foxm1, Skp2, Ezh2, Akt2, Cdkn1a) are misregulated, placing Foxd3 upstream of these proliferative pathways in beta-cells. Pancreas-specific conditional Foxd3 knockout mouse, glucose tolerance testing, beta-cell mass/proliferation measurements, gene expression profiling of isolated islets Endocrinology High 21952247
2013 Foxd3 regulates gene expression in murine ESCs controlling embryonic organ development, epithelium development, and epithelial differentiation; direct targets include Sox4, Safb, Sox15, Fosb, Pmaip1, and Smarcd3, identified following conditional Foxd3 deletion and transcriptome analysis. Conditional Foxd3 deletion, gene expression microarray analysis, validation of novel direct targets Stem cell research Medium 24270162
2020 FOXD3 regulates VISTA (V-domain Ig suppressor of T cell activation) expression in melanoma; BRAF inhibition upregulates FOXD3 and reduces VISTA expression; melanoma cell-specific VISTA expression promotes tumor onset in vivo and is associated with increased T regulatory cells and enhanced PDL-1 on tumor-infiltrating macrophages. FOXD3 manipulation (overexpression/knockdown), VISTA expression analysis, in vivo xenograft model, flow cytometry of tumor-infiltrating immune cells Cell reports Medium 31940493

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 To err (meiotically) is human: the genesis of human aneuploidy. Nature reviews. Genetics 1824 11283700
2009 Apoptosis and cancer: the genesis of a research field. Nature reviews. Cancer 579 19550425
2009 The mammalian ovary from genesis to revelation. Endocrine reviews 557 19776209
2002 Specialized DNA polymerases, cellular survival, and the genesis of mutations. Science (New York, N.Y.) 359 12040171
2005 The genesis and evolution of homeobox gene clusters. Nature reviews. Genetics 349 16341069
2005 Inflammation in the genesis and perpetuation of atrial fibrillation. European heart journal 348 15975993
2004 Timing and topography of cell genesis in the rat retina. The Journal of comparative neurology 308 15164429
2007 MicroRNA expression is required for pancreatic islet cell genesis in the mouse. Diabetes 294 17804764
2004 Cell signaling and the genesis of neuropathic pain. Science's STKE : signal transduction knowledge environment 279 15454629
2007 Effects of RAS on the genesis of embryonal rhabdomyosarcoma. Genes & development 268 17510286
2002 Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo. Genes & development 263 12381664
2001 The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate. Development (Cambridge, England) 238 11684651
2001 Requirement of FoxD3-class signaling for neural crest determination in Xenopus. Development (Cambridge, England) 217 11493569
2008 Genesis and expansion of metazoan transcription factor gene classes. Molecular biology and evolution 194 18296413
2015 Inflammation and its genesis in cystic fibrosis. Pediatric pulmonology 152 26335954
2006 Zebrafish foxd3 is selectively required for neural crest specification, migration and survival. Developmental biology 151 16499899
2000 The pedunculopontine nucleus: its role in the genesis of movement disorders. Yonsei medical journal 138 10817016
2011 Perivascular instruction of cell genesis and fate in the adult brain. Nature neuroscience 127 22030549
2010 Interplay between Foxd3 and Mitf regulates cell fate plasticity in the zebrafish neural crest. Developmental biology 127 20460180
2017 Emerging role for dysregulated decidualization in the genesis of preeclampsia. Placenta 117 28693893
2012 Dynamic and differential regulation of stem cell factor FoxD3 in the neural crest is Encrypted in the genome. PLoS genetics 117 23284303
2012 Genesis of the myofibroblast in lung injury and fibrosis. Proceedings of the American Thoracic Society 108 22802289
2009 Role of cannabis and endocannabinoids in the genesis of schizophrenia. Psychopharmacology 107 19629449
1992 Epinephrine and the genesis of hypertension. Hypertension (Dallas, Tex. : 1979) 104 1309718
1980 Meiosis and ascospore genesis in Neurospora. European journal of cell biology 103 6450683
2014 FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2. Oncotarget 99 24970808
2013 Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3. Proceedings of the National Academy of Sciences of the United States of America 96 23858437
1998 The winged helix transcription factor Hfh2 is expressed in neural crest and spinal cord during mouse development. Mechanisms of development 94 9767163
2011 Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates. Development (Cambridge, England) 92 21228004
2011 Tfap2a and Foxd3 regulate early steps in the development of the neural crest progenitor population. Developmental biology 88 21963426
2006 Sex hormones and the genesis of autoimmunity. Archives of dermatology 87 16549717
2021 Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma. Nature 86 34349258
2008 Regulation of embryonic stem cell self-renewal and pluripotency by Foxd3. Stem cells (Dayton, Ohio) 86 18653770
2000 Dynamic expression of neurotrophin receptors during sensory neuron genesis and differentiation. Developmental biology 84 11071767
1977 Effect of glucan on granulopoiesis and macrophage genesis in mice. Cancer research 84 300652
2019 The genesis and evolution of bead-based multiplexing. Methods (San Diego, Calif.) 82 30659874
2021 The Retromer Complex: From Genesis to Revelations. Trends in biochemical sciences 80 33526371
2020 Singlet Oxygen Metabolism: From Genesis to Signaling. Frontiers in plant science 79 31969891
2016 FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity. Cell stem cell 79 26748757
2014 Genesis and morphogenesis of limb synovial joints and articular cartilage. Matrix biology : journal of the International Society for Matrix Biology 79 25172830
2013 Mesenchymal stem cell transformation and sarcoma genesis. Clinical sarcoma research 79 23880362
2010 Running reduces stress and enhances cell genesis in aged mice. Neurobiology of aging 74 20106549
2010 Mitochondrial protein import and the genesis of steroidogenic mitochondria. Molecular and cellular endocrinology 73 21147195
2020 FOXD3 Regulates VISTA Expression in Melanoma. Cell reports 70 31940493
2019 Genesis of the αβ T-cell receptor. PLoS computational biology 70 30830899
2016 Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification. Cell stem cell 67 26748758
2007 colgate/hdac1 Repression of foxd3 expression is required to permit mitfa-dependent melanogenesis. Developmental biology 64 18068699
2013 FOXD3 is a novel tumor suppressor that affects growth, invasion, metastasis and angiogenesis of neuroblastoma. Oncotarget 63 24269992
2004 Slow axonal transport and the genesis of neuronal morphology. Journal of neurobiology 62 14598366
2017 Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 60 28655711
2013 Onecut1 is essential for horizontal cell genesis and retinal integrity. The Journal of neuroscience : the official journal of the Society for Neuroscience 60 23926259
2021 Gut Microbiota Influence in Hematological Malignancies: From Genesis to Cure. International journal of molecular sciences 59 33498529
2017 Retracted: Risk-Associated Long Noncoding RNA FOXD3-AS1 Inhibits Neuroblastoma Progression by Repressing PARP1-Mediated Activation of CTCF. Molecular therapy : the journal of the American Society of Gene Therapy 58 29398485
2014 Physiological protein aggregation run amuck: stress granules and the genesis of neurodegenerative disease. Discovery medicine 57 24411700
2015 Macrophage and Innate Lymphoid Cell Interplay in the Genesis of Fibrosis. Frontiers in immunology 55 26635811
2011 Adaptive upregulation of FOXD3 and resistance to PLX4032/4720-induced cell death in mutant B-RAF melanoma cells. Oncogene 55 21996740
2023 The genesis of human hematopoietic stem cells. Blood 51 37339578
2016 Role of STAT3 in Genesis and Progression of Human Malignant Gliomas. Molecular neurobiology 51 27660268
2017 FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway. Oncotarget 49 27926503
2015 A Place at the Table: LTD as a Mediator of Memory Genesis. The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry 47 25993993
2014 Using zebrafish to study podocyte genesis during kidney development and regeneration. Genesis (New York, N.Y. : 2000) 47 24920186
2004 Causative and preventive action of calcium in cataracto-genesis. Acta pharmacologica Sinica 46 15456524
1993 The role of gene mutations in the genesis of familial cancers. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 46 8102106
2016 The FOXD3/miR-214/MED19 axis suppresses tumour growth and metastasis in human colorectal cancer. British journal of cancer 39 27811858
2015 The Legacy of Nat Sternberg: The Genesis of Cre-lox Technology. Annual review of virology 39 26958905
2006 Foxd3 mediates zebrafish myf5 expression during early somitogenesis. Developmental biology 39 16386728
2019 Genes CEP55, FOXD3, FOXF2, GNAO1, GRIA4, and KCNA5 as potential diagnostic biomarkers in colorectal cancer. BMC medical genomics 38 30987631
2014 Peroxidasins: novel players in tissue genesis. Trends in biochemical sciences 38 24924147
2011 FOXD3 regulates migration properties and Rnd3 expression in melanoma cells. Molecular cancer research : MCR 38 21478267
1996 Spatiotemporal gradients of cell genesis in the primate retina. Perspectives on developmental neurobiology 38 8931090
2021 Role of inflammatory cytokines in genesis and treatment of atherosclerosis. Trends in cardiovascular medicine 37 33571665
2005 Genesis of ectopic waves: role of coupling, automaticity, and heterogeneity. Biophysical journal 37 16055545
1986 Platelet and vessel wall interaction and the genesis of atherosclerosis. Clinics in haematology 36 2942331
2017 Changing mutational and adaptive landscapes and the genesis of cancer. Biochimica et biophysica acta. Reviews on cancer 34 28167050
2009 Retrotransposons, reverse transcriptase and the genesis of new genetic information. Gene 34 19631262
2023 Genesis of clinical and subclinical endometritis in dairy cows. Reproduction (Cambridge, England) 32 37294111
2021 Genetic control of retinal ganglion cell genesis. Cellular and molecular life sciences : CMLS 30 33782712
2019 Long non-coding RNA FOXD3-AS1 aggravates ischemia/reperfusion injury of cardiomyocytes through promoting autophagy. American journal of translational research 30 31632535
2022 The Subventricular Zone in Glioblastoma: Genesis, Maintenance, and Modeling. Frontiers in oncology 29 35359410
2016 The genesis and presentation of anxiety in disorders of autonomic overexcitation. Autonomic neuroscience : basic & clinical 29 27865628
2020 Immune-mediated genesis of multiple sclerosis. Journal of translational autoimmunity 28 32743522
2014 Oncogenic microRNAs in the genesis of leukemia and lymphoma. Current pharmaceutical design 28 24479800
1975 Genesis of fatty liver and hyperlipemia in the fetal guinea pig. Journal of lipid research 28 1194788
2011 Novel concepts in the genesis of hypertension: role of LOX-1. Cardiovascular drugs and therapy 26 21912849
2011 Loss of Foxd3 results in decreased β-cell proliferation and glucose intolerance during pregnancy. Endocrinology 26 21952247
2022 Creb5 coordinates synovial joint formation with the genesis of articular cartilage. Nature communications 25 36435829
2021 Fractalkine signaling regulates oligodendroglial cell genesis from SVZ precursor cells. Stem cell reports 25 34270934
2012 The role of stem cells and progenitors in the genesis of medulloblastoma. Experimental neurology 25 23178582
2015 FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer. Biochemical and biophysical research communications 24 26341266
2021 Creating custom synthetic genomes in Escherichia coli with REXER and GENESIS. Nature protocols 23 33903757
2021 MiR-328-3p inhibits lung adenocarcinoma-genesis by downregulation PYCR1. Biochemical and biophysical research communications 22 33706104
2013 Transcriptional targets of Foxd3 in murine ES cells. Stem cell research 22 24270162
2010 Functional interaction between Foxd3 and Pax3 in cardiac neural crest development. Genesis (New York, N.Y. : 2000) 22 21254333
2009 Promoter methylation in the genesis of gastrointestinal cancer. Yonsei medical journal 22 19568590
2020 MiR-582-5p Inhibits Bladder Cancer-Genesis by Suppressing TTK Expression. Cancer management and research 21 33244270
2018 Microcalcifications, Their Genesis, Growth, and Biomechanical Stability in Fibrous Cap Rupture. Advances in experimental medicine and biology 21 30315543
2017 Decreased expression of semaphorin 3D is associated with genesis and development in colorectal cancer. World journal of surgical oncology 21 28320475
2015 PAX3 and FOXD3 Promote CXCR4 Expression in Melanoma. The Journal of biological chemistry 21 26205821
2009 Microbial genesis, life and death in glacial ice. Canadian journal of microbiology 21 19190696
1992 Cell-matrix interactions in the genesis of arteriosclerosis and atheroma. Effect of aging. Annals of the New York Academy of Sciences 20 1336648