Gene Symbol: tcf7l1a
Description: transcription factor 7 like 1a
Alias: tcf-3, tcf3, tcf3a, transcription factor 7-like 1-A, HMG box transcription factor 3-A, HMG-box transcription factor, Headless/Tcf3, TCF-3-A, hdl, headless, protein headless, transcription factor 7-like 1a (T-cell specific, HMG-box), transcription factor tcf3, zTcf-3
Species: zebrafish

Top Publications

  1. Lewis J, Bonner J, Modrell M, Ragland J, Moon R, Dorsky R, et al. Reiterated Wnt signaling during zebrafish neural crest development. Development. 2004;131:1299-308 pubmed
    ..Taken together, these results demonstrate that Wnt signals are critical for the initial induction of zebrafish neural crest and suggest that this signaling pathway plays reiterated roles in its development. ..
  2. Wang X, Lee J, Dorsky R. Identification of Wnt-responsive cells in the zebrafish hypothalamus. Zebrafish. 2009;6:49-58 pubmed publisher
    ..These data suggest that canonical Wnt signaling may be functionally required for maintenance of neural progenitor and precursor pools in the embryo, and for ongoing neurogenesis in the adult zebrafish. ..
  3. Bonner J, Gribble S, Veien E, Nikolaus O, Weidinger G, Dorsky R. Proliferation and patterning are mediated independently in the dorsal spinal cord downstream of canonical Wnt signaling. Dev Biol. 2008;313:398-407 pubmed
    ..In contrast, tcf3 gene knockdown results in a reduced mitotic index without affecting dorsal patterning...
  4. Stoick Cooper C, Weidinger G, Riehle K, Hubbert C, Major M, Fausto N, et al. Distinct Wnt signaling pathways have opposing roles in appendage regeneration. Development. 2007;134:479-89 pubmed
    ..These data suggest that Wnt/beta-catenin signaling promotes regeneration, whereas a distinct pathway activated by wnt5b acts in a negative-feedback loop to limit regeneration. ..
  5. Kim C, Oda T, Itoh M, Jiang D, Artinger K, Chandrasekharappa S, et al. Repressor activity of Headless/Tcf3 is essential for vertebrate head formation. Nature. 2000;407:913-6 pubmed
    ..Here we describe the zebrafish headless (hdl) mutant and show that its severe head defects are due to a mutation in T-cell factor-3 (Tcf3), a member of ..
  6. Faro A, Boj S, Ambrósio R, van den Broek O, Korving J, Clevers H. T-cell factor 4 (tcf7l2) is the main effector of Wnt signaling during zebrafish intestine organogenesis. Zebrafish. 2009;6:59-68 pubmed publisher
    ..Single depletion of Tcf1 (tcf7) and Tcf3 (tcf7l1a) function in an Apc mutant background had no effect on endoderm development...
  7. Nyholm M, Wu S, Dorsky R, Grinblat Y. The zebrafish zic2a-zic5 gene pair acts downstream of canonical Wnt signaling to control cell proliferation in the developing tectum. Development. 2007;134:735-46 pubmed
    ..Collectively these findings suggest that Wnts control midbrain proliferation, at least in part, through regulation of two novel target genes, the zic2a-zic5 gene pair. ..
  8. Branam A, Hoffman G, Pelegri F, Greenspan D. Zebrafish chordin-like and chordin are functionally redundant in regulating patterning of the dorsoventral axis. Dev Biol. 2010;341:444-58 pubmed publisher
    ..Loss-of-function experiments demonstrate that Chl serves as a BMP antagonist with functions that overlap and are redundant with those of Chd in forming the dorsoventral axis. ..
  9. Domené S, Roessler E, El Jaick K, Snir M, Brown J, Vélez J, et al. Mutations in the human SIX3 gene in holoprosencephaly are loss of function. Hum Mol Genet. 2008;17:3919-28 pubmed publisher
    ..Our data indicate that SIX3 is a frequent target in the pathogenesis of HPE and demonstrate how this can inform the genetic counseling of families...

More Information


  1. Nyholm M, Abdelilah Seyfried S, Grinblat Y. A novel genetic mechanism regulates dorsolateral hinge-point formation during zebrafish cranial neurulation. J Cell Sci. 2009;122:2137-48 pubmed publisher
  2. Goessling W, North T, Lord A, Ceol C, Lee S, Weidinger G, et al. APC mutant zebrafish uncover a changing temporal requirement for wnt signaling in liver development. Dev Biol. 2008;320:161-74 pubmed publisher
    ..These studies reveal an important and time-dependent role for wnt signaling during liver development and regeneration. ..
  3. Lu F, Sun Y, Wei C, Thisse C, Thisse B. Tissue-specific derepression of TCF/LEF controls the activity of the Wnt/β-catenin pathway. Nat Commun. 2014;5:5368 pubmed publisher
    ..These findings reveal a novel level of regulation of the canonical Wnt/β-catenin signalling pathway occurring in the nucleus and involving tissue-specific derepression of TCF by Lbx2. ..
  4. Jeong J, Einhorn Z, Mathur P, Chen L, Lee S, Kawakami K, et al. Patterning the zebrafish diencephalon by the conserved zinc-finger protein Fezl. Development. 2007;134:127-36 pubmed
    ..Finally, fezl overexpression is able to restore the anterior forebrain and downregulate wnt expression in Headless- and/or Tcf3 (also known as Tcf7l1a)-deficient embryos...
  5. Brunet T, Bouclet A, Ahmadi P, Mitrossilis D, Driquez B, Brunet A, et al. Evolutionary conservation of early mesoderm specification by mechanotransduction in Bilateria. Nat Commun. 2013;4:2821 pubmed publisher
    ..This suggests mesoderm mechanical induction dating back to at least the last bilaterian common ancestor more than 570 million years ago, the period during which mesoderm is thought to have emerged...
  6. Andoniadou C, Signore M, Young R, Gaston Massuet C, Wilson S, Fuchs E, et al. HESX1- and TCF3-mediated repression of Wnt/?-catenin targets is required for normal development of the anterior forebrain. Development. 2011;138:4931-42 pubmed publisher
    ..Here, we show that injection of a hesx1 morpholino into a 'sensitised' zygotic headless (tcf3) mutant background leads to severe forebrain and eye defects, suggesting an interaction between Hesx1 and ..
  7. Ninkovic J, Stigloher C, Lillesaar C, Bally Cuif L. Gsk3beta/PKA and Gli1 regulate the maintenance of neural progenitors at the midbrain-hindbrain boundary in concert with E(Spl) factor activity. Development. 2008;135:3137-48 pubmed publisher
    ..Together, our results suggest a model in which the modulation of E(Spl) and Gsk3beta/PKA activities by Gli1 underlies the dynamic properties of IZ maintenance and recruitment. ..
  8. Bonkowsky J, Wang X, Fujimoto E, Lee J, Chien C, Dorsky R. Domain-specific regulation of foxP2 CNS expression by lef1. BMC Dev Biol. 2008;8:103 pubmed publisher
    ..The foxP2 enhancers we identified will allow dissection of foxP2's role during CNS development. ..
  9. Li S, Esterberg R, Lachance V, Ren D, Radde Gallwitz K, Chi F, et al. Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity. Proc Natl Acad Sci U S A. 2011;108:2264-9 pubmed publisher
    ..Moreover, Rack1 antagonizes canonical Wnt signaling. Together, our data suggest that Rack1 regulates the localization of an essential PCP protein and acts as a molecular switch to promote PCP signaling. ..
  10. Sylvester J, Rich C, Yi C, Peres J, Houart C, Streelman J. Competing signals drive telencephalon diversity. Nat Commun. 2013;4:1745 pubmed publisher
    ..Our data suggest that competing ventral Hedgehog and dorsal Wingless signals mediate evolutionary diversification of the telencephalon. ..
  11. Dohn T, Waxman J. Distinct phases of Wnt/?-catenin signaling direct cardiomyocyte formation in zebrafish. Dev Biol. 2012;361:364-76 pubmed publisher
  12. Goessling W, North T, Loewer S, Lord A, Lee S, Stoick Cooper C, et al. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009;136:1136-47 pubmed publisher
    ..Our work provides in vivo evidence that Wnt activation in stem cells requires PGE2, and suggests the PGE2/Wnt interaction is a master regulator of vertebrate regeneration and recovery. ..
  13. Hüsken U, Stickney H, Gestri G, Bianco I, Faro A, Young R, et al. Tcf7l2 is required for left-right asymmetric differentiation of habenular neurons. Curr Biol. 2014;24:2217-27 pubmed publisher
    ..Tcf7l2 is essential for lateralized fate selection by habenular neurons that can differentiate along two alternative pathways, thereby leading to major neural circuit asymmetries. ..
  14. Hübner K, Grassme K, Rao J, Wenke N, Zimmer C, Korte L, et al. Wnt signaling positively regulates endothelial cell fate specification in the Fli1a-positive progenitor population via Lef1. Dev Biol. 2017;430:142-155 pubmed publisher
    ..Our data indicate a novel role of ?-catenin dependent Wnt signaling in regulating EC specification during vasculogenesis. ..
  15. Lawton A, Nandi A, Stulberg M, Dray N, Sneddon M, Pontius W, et al. Regulated tissue fluidity steers zebrafish body elongation. Development. 2013;140:573-82 pubmed publisher
    ..Modeling and additional data analyses suggest that the balance between the coherence and rate of cell flow determines whether body elongation is linear or whether congestion forms within the flow and the body axis becomes contorted. ..
  16. Matsuda M, Nogare D, Somers K, Martin K, Wang C, Chitnis A. Lef1 regulates Dusp6 to influence neuromast formation and spacing in the zebrafish posterior lateral line primordium. Development. 2013;140:2387-97 pubmed publisher
    ..This is associated with progressively slower PLLp migration, reduced spacing between deposited neuromasts and premature termination of the PLLp system. ..
  17. Hino H, Nakanishi A, Seki R, Aoki T, Yamaha E, Kawahara A, et al. Roles of maternal wnt8a transcripts in axis formation in zebrafish. Dev Biol. 2018;434:96-107 pubmed publisher
    ..Finally, we re-examined the maternal wnt genes and found that Wnt6a is an alternative candidate DD. ..
  18. Lin J, Wang X, Dorsky R. Progenitor expansion in apc mutants is mediated by Jak/Stat signaling. BMC Dev Biol. 2011;11:73 pubmed publisher
    ..Together, our data suggest that the regulation of Jak/Stat signaling may represent a conserved mechanism explaining the expansion of undifferentiated cells downstream of APC mutations. ..
  19. Danesin C, Peres J, Johansson M, Snowden V, Cording A, Papalopulu N, et al. Integration of telencephalic Wnt and hedgehog signaling center activities by Foxg1. Dev Cell. 2009;16:576-87 pubmed publisher
    ..Altogether, these findings identify a key direct target of Foxg1, and uncover a simple molecular mechanism by which Foxg1 integrates two opposing signaling centers. ..
  20. Piloto S, Schilling T. Ovo1 links Wnt signaling with N-cadherin localization during neural crest migration. Development. 2010;137:1981-90 pubmed publisher
    ..Similar processes probably occur in other cell types in which Wnt signaling promotes migration. ..
  21. Vibert L, Aquino G, Gehring I, Subkankulova T, Schilling T, Rocco A, et al. An ongoing role for Wnt signaling in differentiating melanocytes in vivo. Pigment Cell Melanoma Res. 2017;30:219-232 pubmed publisher
    ..Downregulation of Wnt signaling also results in altered melanocyte morphology and organization. We conclude that Wnt signaling plays a role in regulating ongoing aspects of melanocyte differentiation in zebrafish. ..
  22. Gribble S, Kim H, Bonner J, Wang X, Dorsky R. Tcf3 inhibits spinal cord neurogenesis by regulating sox4a expression. Development. 2009;136:781-9 pubmed publisher
    The Lef/Tcf factor Tcf3 is expressed throughout the developing vertebrate central nervous system (CNS), but its function and transcriptional targets are uncharacterized...
  23. Kapsimali M, Caneparo L, Houart C, Wilson S. Inhibition of Wnt/Axin/beta-catenin pathway activity promotes ventral CNS midline tissue to adopt hypothalamic rather than floorplate identity. Development. 2004;131:5923-33 pubmed
  24. Dorsky R, Snyder A, Cretekos C, Grunwald D, Geisler R, Haffter P, et al. Maternal and embryonic expression of zebrafish lef1. Mech Dev. 1999;86:147-50 pubmed
    ..In addition, we cloned two tcf3 genes and a homolog of tcf4, neither of which were strongly expressed in premigratory neural crest.
  25. Fernandes A, Fero K, Arrenberg A, Bergeron S, Driever W, Burgess H. Deep brain photoreceptors control light-seeking behavior in zebrafish larvae. Curr Biol. 2012;22:2042-7 pubmed publisher
    ..Our findings shed light on the identity and function of deep brain photoreceptors and suggest that otpa specifies an ancient population of sensory neurons that mediate behavioral responses to light. ..
  26. Kim H, Dorsky R. Tcf7l1 is required for spinal cord progenitor maintenance. Dev Dyn. 2011;240:2256-64 pubmed publisher
    ..In this study, we have investigated the role of Tcf7l1 (formerly named Tcf3) in maintaining spinal progenitor characteristics and allowing the continued production of neurons and glia ..
  27. McGraw H, Drerup C, Culbertson M, Linbo T, Raible D, Nechiporuk A. Lef1 is required for progenitor cell identity in the zebrafish lateral line primordium. Development. 2011;138:3921-30 pubmed publisher
    ..These findings revealed a novel role for the Wnt signaling pathway during mechanosensory organ formation in zebrafish. ..
  28. Yin A, Korzh S, Winata C, Korzh V, Gong Z. Wnt signaling is required for early development of zebrafish swimbladder. PLoS ONE. 2011;6:e18431 pubmed publisher
    ..We also demonstrated that genes encoding Wnt signaling members Wnt5b, Fz2, Fz7b, Lef1, Tcf3 were expressed in different layers of swimbladder...
  29. Kim S, Chung A, Kim D, Kim Y, Kim H, Kwon H, et al. Tcf3 function is required for the inhibition of oligodendroglial fate specification in the spinal cord of zebrafish embryos. Mol Cells. 2011;32:383-8 pubmed publisher
    ..This study shows that Tcf3, a member of the Lef/Tcf family of proteins, is required to inhibit the premature oligodendroglial fate ..
  30. Thorpe C, Moon R. nemo-like kinase is an essential co-activator of Wnt signaling during early zebrafish development. Development. 2004;131:2899-909 pubmed
    ..We show that overexpressed zebrafish nlk, in concert with wnt8, can downregulate two tcf3 homologs, tcf3a and tcf3b, that repress Wnt targets during neurectodermal patterning...
  31. Ro H, Dawid I. Modulation of Tcf3 repressor complex composition regulates cdx4 expression in zebrafish. EMBO J. 2011;30:2894-907 pubmed publisher
    ..Here, we provide evidence that Tcf3 suppresses cdx4 expression through direct binding to multiple sites in the cdx4 gene regulatory region...
  32. Sorrell M, Dohn T, D Aniello E, Waxman J. Tcf7l1 proteins cell autonomously restrict cardiomyocyte and promote endothelial specification in zebrafish. Dev Biol. 2013;380:199-210 pubmed publisher
    ..In contrast to partially redundant roles in anterior neural patterning, we find that Tcf7l1a and Tcf7l1b have non-redundant functions with respect to restricting CM specification during anterior mesodermal ..
  33. Pelegri F. Maternal factors in zebrafish development. Dev Dyn. 2003;228:535-54 pubmed
  34. Cavodeassi F, Carreira Barbosa F, Young R, Concha M, Allende M, Houart C, et al. Early stages of zebrafish eye formation require the coordinated activity of Wnt11, Fz5, and the Wnt/beta-catenin pathway. Neuron. 2005;47:43-56 pubmed
  35. zhan G, Sezgin E, Wehner D, Pfister A, K hl S, Kagermeier Schenk B, et al. Lypd6 enhances Wnt/?-catenin signaling by promoting Lrp6 phosphorylation in raft plasma membrane domains. Dev Cell. 2013;26:331-45 pubmed publisher
    ..Thus, Lypd6 appears to control Lrp6 activation specifically in membrane rafts, which is essential for downstream signaling...
  36. Devakanmalai G, Zumrut H, Ozbudak E. Cited3 activates Mef2c to control muscle cell differentiation and survival. Biol Open. 2013;2:505-14 pubmed publisher
    ..Our findings demonstrate that Cited3 is a critical transcriptional coactivator functioning during muscle differentiation and its absence leads to defects in terminal differentiation and survival of muscle cells. ..
  37. Wang X, Kopinke D, Lin J, McPherson A, Duncan R, Otsuna H, et al. Wnt signaling regulates postembryonic hypothalamic progenitor differentiation. Dev Cell. 2012;23:624-36 pubmed publisher
    ..This study establishes the vertebrate hypothalamus as a model for Wnt-regulated postembryonic neural progenitor differentiation and defines specific roles for Wnt signaling in neurogenesis. ..
  38. Head J, Gacioch L, Pennisi M, Meyers J. Activation of canonical Wnt/?-catenin signaling stimulates proliferation in neuromasts in the zebrafish posterior lateral line. Dev Dyn. 2013;242:832-46 pubmed publisher
    ..These data suggest that Wnt/?-catenin signaling is both necessary and sufficient for the control of proliferation of lateral line progenitors during development, ongoing growth of the neuromasts, and hair cell regeneration. ..
  39. Aman A, Piotrowski T. Wnt/beta-catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression. Dev Cell. 2008;15:749-61 pubmed publisher
    ..Although the Fgf, Wnt/beta-catenin, and chemokine signaling pathways are well known to be involved in cancer progression, these studies provide in vivo evidence that these pathways are functionally linked. ..
  40. Hardy M, Ross L, Chien C. Focal gene misexpression in zebrafish embryos induced by local heat shock using a modified soldering iron. Dev Dyn. 2007;236:3071-6 pubmed
    ..We have validated this method in three stable transgenic lines and at three developmental timepoints. Local heat shock is a fast, easy, and inexpensive method for gene misexpression. ..
  41. Kent M, Buchner C, Watral V, Sanders J, Ladu J, Peterson T, et al. Development and maintenance of a specific pathogen-free (SPF) zebrafish research facility for Pseudoloma neurophilia. Dis Aquat Organ. 2011;95:73-9 pubmed publisher
    ..neurophilia. Thus, we have established 9 lines of zebrafish SPF for P. neurophilia. However, 26 fish exhibited mycobacteriosis, with acid-fast bacteria present in tissue sections, and 49 other fish had incidental lesions. ..
  42. Valdivia L, Young R, Hawkins T, Stickney H, Cavodeassi F, Schwarz Q, et al. Lef1-dependent Wnt/?-catenin signalling drives the proliferative engine that maintains tissue homeostasis during lateral line development. Development. 2011;138:3931-41 pubmed publisher
    ..Our data support a model in which Lef1 sustains proliferation of leading zone progenitors, maintaining the primordium size and defining neuromast deposition rate. ..
  43. Tawk M, Makoukji J, Belle M, Fonte C, Trousson A, Hawkins T, et al. Wnt/beta-catenin signaling is an essential and direct driver of myelin gene expression and myelinogenesis. J Neurosci. 2011;31:3729-42 pubmed publisher
    ..The present findings attribute to Wnt/?-catenin pathway components an essential role in myelin gene expression and myelinogenesis. ..
  44. Meyers J, Hu L, Moses A, Kaboli K, Papandrea A, Raymond P. ?-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina. Neural Dev. 2012;7:30 pubmed publisher
    ..This suggests that the ?-catenin/Wnt cascade is part of the shared molecular circuitry that maintains retinal stem cells for both homeostatic growth and epimorphic regeneration. ..
  45. Shimizu N, Kawakami K, Ishitani T. Visualization and exploration of Tcf/Lef function using a highly responsive Wnt/?-catenin signaling-reporter transgenic zebrafish. Dev Biol. 2012;370:71-85 pubmed publisher
    ..Thus, these reporter lines are highly useful tools for studying Tcf/Lef-mediated Wnt/?-catenin signaling-dependent processes. ..
  46. Hoage T, Sun X, Xu X. Functions of the Wnt/?-catenin pathway in an anemia-induced zebrafish model of cardiomyopathy are location dependent. Biochem Biophys Res Commun. 2011;415:490-6 pubmed publisher
  47. Hofsteen P, Robitaille A, Chapman D, Moon R, Murry C. Quantitative proteomics identify DAB2 as a cardiac developmental regulator that inhibits WNT/β-catenin signaling. Proc Natl Acad Sci U S A. 2016;113:1002-7 pubmed publisher
    ..Our work demonstrates that quantifying the proteome of human stem cells can identify previously unknown developmental regulators. ..
  48. Mathew L, Sengupta S, Franzosa J, Perry J, La Du J, Andreasen E, et al. Comparative expression profiling reveals an essential role for raldh2 in epimorphic regeneration. J Biol Chem. 2009;284:33642-53 pubmed publisher
    ..Expression of raldh2 is regulated by Wnt and fibroblast growth factor/ERK signaling. ..
  49. Caneparo L, Huang Y, Staudt N, Tada M, Ahrendt R, Kazanskaya O, et al. Dickkopf-1 regulates gastrulation movements by coordinated modulation of Wnt/beta catenin and Wnt/PCP activities, through interaction with the Dally-like homolog Knypek. Genes Dev. 2007;21:465-80 pubmed
    ..Our data therefore indicate that Dkk1 regulates gastrulation movement through interaction with LRP5/6 and Kny and coordinated modulations of Wnt/beta catenin and Wnt/PCP pathways. ..
  50. 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. ..
  51. Mahmoudi T, Boj S, Hatzis P, Li V, Taouatas N, Vries R, et al. The leukemia-associated Mllt10/Af10-Dot1l are Tcf4/?-catenin coactivators essential for intestinal homeostasis. PLoS Biol. 2010;8:e1000539 pubmed publisher
    ..The methyltransferase DOT1L may present an attractive candidate for drug targeting in colorectal cancer. ..
  52. Martin B, Kimelman D. Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation. Dev Cell. 2008;15:121-33 pubmed publisher
    ..We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates...