Gene Symbol: Foxd3
Description: forkhead box D3
Alias: CWH3, Genesis, Hfh2, forkhead box protein D3, HFH-2, HNF-3/forkhead homolog 2, HNF3/FH transcription factor genesis, hepatocyte nuclear factor 3 forkhead homolog 2
Species: mouse
Products:     Foxd3

Top Publications

  1. Dottori M, Gross M, Labosky P, Goulding M. The winged-helix transcription factor Foxd3 suppresses interneuron differentiation and promotes neural crest cell fate. Development. 2001;128:4127-38 pubmed
    ..In this study, we show that the winged helix transcription factor Foxd3 is expressed in both premigratory and migratory neural crest cells...
  2. Mundell N, Labosky P. Neural crest stem cell multipotency requires Foxd3 to maintain neural potential and repress mesenchymal fates. Development. 2011;138:641-52 pubmed publisher
    ..Our earlier work demonstrated that Foxd3 is required for maintenance of NC progenitors in the embryo...
  3. Respuela P, Nikolić M, Tan M, Frommolt P, Zhao Y, Wysocka J, et al. Foxd3 Promotes Exit from Naive Pluripotency through Enhancer Decommissioning and Inhibits Germline Specification. Cell Stem Cell. 2016;18:118-33 pubmed publisher
    ..regulatory principles orchestrating peri-implantation development, here we show that the transcription factor Foxd3 is necessary for exit from naive pluripotency and progression to a primed pluripotent state...
  4. Zhu L, Zhang S, Jin Y. Foxd3 suppresses NFAT-mediated differentiation to maintain self-renewal of embryonic stem cells. EMBO Rep. 2014;15:1286-96 pubmed publisher
    Pluripotency-associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, molecular mechanisms underlying its function are largely unknown...
  5. Ramos C, Rocha S, Gaspar C, Henrique D. Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord. PLoS ONE. 2010;5:e15515 pubmed publisher
    ..However, Jag1 can only activate Notch signalling within the V1 and dI6 domains, whereas Dll1 can signal to neural progenitors both inside and outside its domains of expression. ..
  6. Espinosa Medina I, Outin E, Picard C, Chettouh Z, Dymecki S, Consalez G, et al. Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors. Science. 2014;345:87-90 pubmed publisher
    ..Thus, cranial Schwann cell precursors are the source of parasympathetic neurons during normal development. ..
  7. Adameyko I, Lallemend F, Furlan A, Zinin N, Aranda S, Kitambi S, et al. Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest. Development. 2012;139:397-410 pubmed publisher
  8. Plank J, Mundell N, Frist A, Legrone A, Kim T, Musser M, et al. Influence and timing of arrival of murine neural crest on pancreatic beta cell development and maturation. Dev Biol. 2011;349:321-30 pubmed publisher
    ..Using a neural crest-specific deletion of the Forkhead transcription factor Foxd3, we ablated neural crest cells that migrate to the pancreatic primordium...
  9. Liu Y, Labosky P. Regulation of embryonic stem cell self-renewal and pluripotency by Foxd3. Stem Cells. 2008;26:2475-84 pubmed publisher
    The Foxd3 forkhead transcription factor is required for maintaining pluripotent cells in the early mouse embryo and for the establishment of murine embryonic stem cell (ESC) lines...

More Information


  1. Mundell N, Plank J, Legrone A, Frist A, Zhu L, Shin M, et al. Enteric nervous system specific deletion of Foxd3 disrupts glial cell differentiation and activates compensatory enteric progenitors. Dev Biol. 2012;363:373-87 pubmed publisher
    ..Our earlier work demonstrated that the transcription factor Foxd3 is required early in neural crest-derived progenitors for self-renewal, multipotency and establishment of multiple ..
  2. Mittal A, Pulina M, Hou S, Astrof S. Fibronectin and integrin alpha 5 play essential roles in the development of the cardiac neural crest. Mech Dev. 2010;127:472-84 pubmed publisher
    ..However, we found that FN and integrin ?5 modulate CNC proliferation and survival, and are required for the presence of normal numbers of CNC cells at their destinations. ..
  3. Anderson M, Schimmang T, Lewandoski M. An FGF3-BMP Signaling Axis Regulates Caudal Neural Tube Closure, Neural Crest Specification and Anterior-Posterior Axis Extension. PLoS Genet. 2016;12:e1006018 pubmed publisher
    ..Uncovering this FGF3-BMP signaling axis is a major advance toward understanding how these tissue layers interact during axis extension with important implications in human disease. ..
  4. Horner V, Caspary T. Disrupted dorsal neural tube BMP signaling in the cilia mutant Arl13b hnn stems from abnormal Shh signaling. Dev Biol. 2011;355:43-54 pubmed publisher
    ..We demonstrate that Arl13b is required non-autonomously for BMP signaling and Wnt ligand expression, indicating that the abnormal Shh signaling environment in Arl13b(hnn) embryos indirectly causes dorsal defects. ..
  5. Yan J, Zhao C, Ding L, Zhou X. FOXD3 suppresses tumor growth and angiogenesis in non-small cell lung cancer. Biochem Biophys Res Commun. 2015;466:111-6 pubmed publisher
    The transcription factor forkhead box D3 (FOXD3), widely studied as a transcriptional repressor in embryogenesis, participates in the carcinogenesis of many cancers...
  6. Kriks S, Lanuza G, Mizuguchi R, Nakafuku M, Goulding M. Gsh2 is required for the repression of Ngn1 and specification of dorsal interneuron fate in the spinal cord. Development. 2005;132:2991-3002 pubmed
    ..Our results provide evidence that genetic interactions involving repression of Ngn1 by Gsh2 promote the differentiation of dI3 neurons from class A progenitors. ..
  7. Pasek R, Gannon M. Advancements and challenges in generating accurate animal models of gestational diabetes mellitus. Am J Physiol Endocrinol Metab. 2013;305:E1327-38 pubmed publisher
    ..Continued development of animal models of GDM is essential for understanding the consequences of this disease as well as providing insights into potential treatments and preventative measures. ..
  8. Ding Y, Kim J, Xu Y, Rao Y, Chen Z. Ventral migration of early-born neurons requires Dcc and is essential for the projections of primary afferents in the spinal cord. Development. 2005;132:2047-56 pubmed
  9. Gross M, Dottori M, Goulding M. Lbx1 specifies somatosensory association interneurons in the dorsal spinal cord. Neuron. 2002;34:535-49 pubmed
    ..Lbx1, therefore, plays a critical role in the development of sensory pathways in the spinal cord that relay pain and touch. ..
  10. Masek J, Machon O, Korinek V, Taketo M, Kozmik Z. Tcf7l1 protects the anterior neural fold from adopting the neural crest fate. Development. 2016;143:2206-16 pubmed publisher
    ..This reduces the developing prosencephalon without affecting the anterior-posterior neural character. Thus, Tcf7l1 defines the border between the NC and the prospective forebrain via restriction of the Wnt/?-catenin signaling gradient. ..
  11. Liber D, Domaschenz R, Holmqvist P, Mazzarella L, Georgiou A, Leleu M, et al. Epigenetic priming of a pre-B cell-specific enhancer through binding of Sox2 and Foxd3 at the ESC stage. Cell Stem Cell. 2010;7:114-26 pubmed publisher
    ..Binding of Foxd3 suppresses intergenic transcription of the enhancer and surrounding sequences...
  12. Fujita K, Ogawa R, Ito K. CHD7, Oct3/4, Sox2, and Nanog control FoxD3 expression during mouse neural crest-derived stem cell formation. FEBS J. 2016;283:3791-3806 pubmed publisher
    ..In the present study, we analyzed a regulatory gene cascade in the formation of mouse NCSCs. The inhibition of FoxD3 expression significantly suppressed the expression of Sox10, which is an indispensable transcription factor for ..
  13. Clevidence D, Overdier D, Tao W, Qian X, Pani L, Lai E, et al. Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family. Proc Natl Acad Sci U S A. 1993;90:3948-52 pubmed
    ..The HNF-3/fkh motif therefore comprises a large gene family of transcription factors that play a role in tissue-specific gene regulation and development. ..
  14. Nelms B, Pfaltzgraff E, Labosky P. Functional interaction between Foxd3 and Pax3 in cardiac neural crest development. Genesis. 2011;49:10-23 pubmed publisher
    The transcription factors Foxd3 and Pax3 are important early regulators of neural crest (NC) progenitor cell properties...
  15. Nitzan E, Pfaltzgraff E, Labosky P, Kalcheim C. Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3. Proc Natl Acad Sci U S A. 2013;110:12709-14 pubmed publisher
    ..Furthermore, although both populations are initially part of the Foxd3 lineage, hypaxial melanocytes lose Foxd3 at late stages upon separation from the nerve, whereas we recently found ..
  16. Cheng A, Li M, Kang W, Cheng V, Chou J, Lau S, et al. Helicobacter pylori causes epigenetic dysregulation of FOXD3 to promote gastric carcinogenesis. Gastroenterology. 2013;144:122-133.e9 pubmed publisher
    ..Promoter hypermethylation occurs during Helicobacter pylori-induced gastritis. We investigated whether the deregulated genes contribute to gastric tumorigenesis...
  17. Machon O, Masek J, Machonova O, Krauss S, Kozmik Z. Meis2 is essential for cranial and cardiac neural crest development. BMC Dev Biol. 2015;15:40 pubmed publisher
    ..Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse. ..
  18. Zaret K. Developmental competence of the gut endoderm: genetic potentiation by GATA and HNF3/fork head proteins. Dev Biol. 1999;209:1-10 pubmed
    ..The mechanistic implications of genetic potentiation and its general significance are discussed. ..
  19. Mesnard D, Constam D. Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst. J Cell Biol. 2010;191:129-39 pubmed publisher
    ..The unprecedented sensitivity and spatial resolution of CLIP opens exciting new possibilities to elucidate PC functions in vivo. ..
  20. Krentz A, Murphy M, Zhang T, Sarver A, Jain S, Griswold M, et al. Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Dev Biol. 2013;377:67-78 pubmed publisher
    ..Given the strong evidence for involvement of DMRT1 in human TGCT, the downstream genes and pathways identified in this study provide potentially useful candidates for roles in the human disease. ..
  21. Xu D, Yoder M, Sutton J, Hromas R. Forced expression of Genesis, a winged helix transcriptional repressor isolated from embryonic stem cells, blocks granulocytic differentiation of 32D myeloid cells. Leukemia. 1998;12:207-12 pubmed
    ..a novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis. Genesis was found to be a transcriptional repressor expressed almost exclusively in embryonic stem cells or ..
  22. Zechner D, Muller T, Wende H, Walther I, Taketo M, Crenshaw E, et al. Bmp and Wnt/beta-catenin signals control expression of the transcription factor Olig3 and the specification of spinal cord neurons. Dev Biol. 2007;303:181-90 pubmed
    ..We conclude that Wnt/beta-catenin and BMP signals coordinately control the specification of dorsal neurons in the spinal cord. ..
  23. Landgren H, Carlsson P. FoxJ3, a novel mammalian forkhead gene expressed in neuroectoderm, neural crest, and myotome. Dev Dyn. 2004;231:396-401 pubmed
    ..Developing limbs have a complex pattern of Foxj3 expression that at E12.5 colocalizes with the condensed mesenchyme of the skeletal primordia. ..
  24. Krishnakumar R, Chen A, Pantovich M, Danial M, Parchem R, Labosky P, et al. FOXD3 Regulates Pluripotent Stem Cell Potential by Simultaneously Initiating and Repressing Enhancer Activity. Cell Stem Cell. 2016;18:104-17 pubmed publisher
    ..during differentiation of embryonic stem to epiblast cells and uncovered the forkhead transcription factor FOXD3 as a major regulator of the developmental potential of both pluripotent states...
  25. Stam F, Hendricks T, Zhang J, Geiman E, Francius C, Labosky P, et al. Renshaw cell interneuron specialization is controlled by a temporally restricted transcription factor program. Development. 2012;139:179-90 pubmed publisher
    ..The development of RCs is additionally dependent on the forkhead transcription factor Foxd3, which is more broadly expressed in postmitotic V1 interneurons...
  26. Baksi S, Jana N, Bhattacharyya N, Mukhopadhyay D. Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin. PLoS ONE. 2013;8:e76792 pubmed publisher
    ..Grb2 overexpression was predominantly regulated by the transcription factor Forkhead Box D3 (Foxd3). Exogenous expression of Grb2 also reduced aggregation of mutant Htt in Neuro2A cells...
  27. Perera H, Caldwell M, Hayes Patterson D, Teng L, Peshavaria M, Jetton T, et al. Expression and shifting subcellular localization of the transcription factor, Foxd3, in embryonic and adult pancreas. Gene Expr Patterns. 2006;6:971-7 pubmed
    ..b>Foxd3, a member of the forkhead family of transcriptional regulators, is required for the maintenance of embryonic stem ..
  28. Hanna L, Foreman R, Tarasenko I, Kessler D, Labosky P. Requirement for Foxd3 in maintaining pluripotent cells of the early mouse embryo. Genes Dev. 2002;16:2650-61 pubmed
    ..Here, we report that Foxd3, a member of the forkhead family of transcriptional regulators, is required for maintenance of embryonic cells of ..
  29. Makki N, Capecchi M. Cardiovascular defects in a mouse model of HOXA1 syndrome. Hum Mol Genet. 2012;21:26-31 pubmed publisher
    ..Thus, our data allow us to suggest a model in which Hoxa1 regulates heart development through its influence on cardiac NCCs, providing insight into the mechanisms underlying the human disease. ..
  30. Suflita M, Pfaltzgraff E, Mundell N, Pevny L, Labosky P. Ground-state transcriptional requirements for skin-derived precursors. Stem Cells Dev. 2013;22:1779-88 pubmed publisher
    ..Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs...
  31. Sanchez Ferras O, Bernas G, Farnos O, Touré A, Souchkova O, Pilon N. A direct role for murine Cdx proteins in the trunk neural crest gene regulatory network. Development. 2016;143:1363-74 pubmed publisher least in part, directly controlling the expression of the key early regulators of NC ontogenesis Pax3,Msx1 and Foxd3 Our work thus reveals a novel role for Cdx proteins at the top of the trunk NC gene regulatory network in the ..
  32. Zhang D, Lee H, Haspel J, Jin Y. Long noncoding RNA FOXD3-AS1 regulates oxidative stress-induced apoptosis via sponging microRNA-150. FASEB J. 2017;31:4472-4481 pubmed publisher
    ..Our studies identified a highly up-regulated mammalian lncRNA, FOXD3-AS1, known as linc1623 in mice, in the setting of hyperoxia/reactive oxygen species (ROS)-induced lung ..
  33. Teng L, Mundell N, Frist A, Wang Q, Labosky P. Requirement for Foxd3 in the maintenance of neural crest progenitors. Development. 2008;135:1615-24 pubmed publisher
    ..b>Foxd3 is required early in mouse embryogenesis; Foxd3(-/-) embryos fail around the time of implantation, cells of the ..
  34. Tompers D, Foreman R, Wang Q, Kumanova M, Labosky P. Foxd3 is required in the trophoblast progenitor cell lineage of the mouse embryo. Dev Biol. 2005;285:126-37 pubmed
    ..The transcriptional repressor Foxd3 is required for maintenance of the epiblast and the in vitro establishment of embryonic stem cell lines...
  35. Gard C, Gonzalez Curto G, Frarma Y, Chollet E, Duval N, Auzié V, et al. Pax3- and Pax7-mediated Dbx1 regulation orchestrates the patterning of intermediate spinal interneurons. Dev Biol. 2017;432:24-33 pubmed publisher
    ..Furthermore, our data supports the model whereby cell fate choices in the neural tube do not rely on binary decisions but rather on inhibition of multiple alternative fates. ..
  36. Nitzan E, Krispin S, Pfaltzgraff E, Klar A, Labosky P, Kalcheim C. A dynamic code of dorsal neural tube genes regulates the segregation between neurogenic and melanogenic neural crest cells. Development. 2013;140:2269-79 pubmed publisher
    ..Analysis of progenitors expressing a Foxd3 reporter reveals that prospective melanoblasts downregulate Foxd3 and have already segregated from neural lineages ..
  37. Reinert R, Cai Q, Hong J, Plank J, Aamodt K, Prasad N, et al. Vascular endothelial growth factor coordinates islet innervation via vascular scaffolding. Development. 2014;141:1480-91 pubmed publisher
  38. Kaartinen V, Dudas M, Nagy A, Sridurongrit S, Lu M, Epstein J. Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Development. 2004;131:3481-90 pubmed
    ..Thus, the type I BMP receptor ALK2 plays an essential cell-autonomous role in the development of the cardiac outflow tract and aortic arch derivatives. ..
  39. Elms P, Siggers P, Napper D, Greenfield A, Arkell R. Zic2 is required for neural crest formation and hindbrain patterning during mouse development. Dev Biol. 2003;264:391-406 pubmed
    ..This work provides the first genetic evidence that the Zic genes are involved in neural crest production and the first demonstration that Zic2 functions during hindbrain patterning. ..
  40. Mesnard D, Donnison M, Fuerer C, Pfeffer P, Constam D. The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities. Genes Dev. 2011;25:1871-80 pubmed publisher
    ..Adding cell-cell communication to the pleiotropic portfolio of these proteases provides a new framework to study proprotein processing also in other relevant contexts. ..
  41. Miesegaes G, Klisch T, Thaller C, Ahmad K, Atkinson R, Zoghbi H. Identification and subclassification of new Atoh1 derived cell populations during mouse spinal cord development. Dev Biol. 2009;327:339-51 pubmed publisher
    ..Altogether we reveal the existence of multiple Atoh1 dependent cell types in the spinal cord, and uncover a novel progenitor domain that arises late in development. ..
  42. Ma Q, Fode C, Guillemot F, Anderson D. Neurogenin1 and neurogenin2 control two distinct waves of neurogenesis in developing dorsal root ganglia. Genes Dev. 1999;13:1717-28 pubmed
    ..These data reveal remarkable parallels in the roles of bHLH factors during neurogenesis in the DRG, and myogenesis in the neighboring myotome. ..
  43. Muller T, Anlag K, Wildner H, Britsch S, Treier M, Birchmeier C. The bHLH factor Olig3 coordinates the specification of dorsal neurons in the spinal cord. Genes Dev. 2005;19:733-43 pubmed
    ..We conclude that Olig3 expression distinguishes the two major classes of progenitors in the dorsal spinal cord and determines the distinct specification program of class A neurons. ..
  44. Sutton J, Costa R, Klug M, Field L, Xu D, Largaespada D, et al. Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells. J Biol Chem. 1996;271:23126-33 pubmed
    A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized...
  45. Bondurand N, Southard Smith E. Mouse models of Hirschsprung disease and other developmental disorders of the enteric nervous system: Old and new players. Dev Biol. 2016;417:139-57 pubmed publisher
    ..Finally, because HSCR has become a paradigm for complex oligogenic diseases with non-Mendelian inheritance, the importance of gene interactions, modifier genes, and initial studies on genetic background effects are outlined. ..
  46. Kam M, Cheung M, Zhu J, Cheng W, Sat E, Tam P, et al. Homeobox b5 (Hoxb5) regulates the expression of Forkhead box D3 gene (Foxd3) in neural crest. Int J Biochem Cell Biol. 2014;55:144-52 pubmed publisher
    ..Current study showed that both the human and mouse Foxd3 promoters were bound and trans-activated by Hoxb5 in NC-derived neuroblastoma cells...
  47. Yu J, Holland N, Holland L. An amphioxus winged helix/forkhead gene, AmphiFoxD: insights into vertebrate neural crest evolution. Dev Dyn. 2002;225:289-97 pubmed
    ..Phylogenetic analysis indicates that the AmphiFoxD is basal to vertebrate FoxD1, FoxD2, FoxD3, FoxD4, and FoxD5. One of these vertebrate genes (FoxD3) consistently marks neural crest during development...
  48. Clevidence D, Overdier D, Peterson R, Porcella A, Ye H, Paulson K, et al. Members of the HNF-3/forkhead family of transcription factors exhibit distinct cellular expression patterns in lung and regulate the surfactant protein B promoter. Dev Biol. 1994;166:195-209 pubmed
    ..Our results suggest that SPB promoter activity is regulated by HNF-3 alpha and HFH-8 proteins in a cell type-specific manner. ..
  49. Gosgnach S, Lanuza G, Butt S, Saueressig H, Zhang Y, Velasquez T, et al. V1 spinal neurons regulate the speed of vertebrate locomotor outputs. Nature. 2006;440:215-9 pubmed
  50. Plank J, Suflita M, Galindo C, Labosky P. Transcriptional targets of Foxd3 in murine ES cells. Stem Cell Res. 2014;12:233-40 pubmed publisher
    ..The transcription factor Foxd3 is critical for maintenance of self-renewal, survival, and pluripotency in murine embryonic stem cells (ESCs)...
  51. Andoniadou C, Signore M, Sajedi E, Gaston Massuet C, Kelberman D, Burns A, et al. Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development. 2007;134:1499-508 pubmed
    ..However, conditional expression of Hesx1 within the AFB can rescue the forebrain defects observed in the Hesx1 mutants. The results presented here provide new insights into the function of Hesx1 in forebrain formation. ..
  52. Labosky P, Kaestner K. The winged helix transcription factor Hfh2 is expressed in neural crest and spinal cord during mouse development. Mech Dev. 1998;76:185-90 pubmed
    ..Here we demonstrate that Hfh2 (HNF3 forkhead homologue 2), a member of the 'winged helix' or 'forkhead' transcription factor gene family, is ..
  53. Zhang Y, Wang Z, Xiao H, Liu X, Zhu G, Yu D, et al. Foxd3 suppresses interleukin-10 expression in B cells. Immunology. 2017;150:478-488 pubmed publisher
    ..predict transcription factors binding the IL-10 promoter and found that IL-10 promoter had many binding sites for Foxd3. Chromatin immunoprecipitation PCR assay demonstrated that Foxd3 directly binds the predicted binding sites around ..
  54. Buckley D, Burroughs Garcia J, Lewandoski M, Waters S. Characterization of the Gbx1-/- mouse mutant: a requirement for Gbx1 in normal locomotion and sensorimotor circuit development. PLoS ONE. 2013;8:e56214 pubmed publisher
    ..The generation of this null allele has enabled us to functionally characterize a novel role for Gbx1 in development of the spinal cord. ..
  55. Storm R, Cholewa Waclaw J, Reuter K, Bröhl D, Sieber M, Treier M, et al. The bHLH transcription factor Olig3 marks the dorsal neuroepithelium of the hindbrain and is essential for the development of brainstem nuclei. Development. 2009;136:295-305 pubmed publisher
    ..Climbing fiber neurons of the inferior olivary nucleus express Foxd3 and require Olig3 as well as Ptf1a for the determination of their fate...
  56. Plank J, Frist A, Legrone A, Magnuson M, Labosky P. Loss of Foxd3 results in decreased ?-cell proliferation and glucose intolerance during pregnancy. Endocrinology. 2011;152:4589-600 pubmed publisher
    ..The transcription factor Forkhead box D3 (Foxd3) is required for maintenance and self-renewal of several diverse progenitor cell lineages, and Foxd3 is expressed ..