Gene Symbol: Tcf15
Description: transcription factor 15
Alias: Meso1, bHLH-EC2, transcription factor 15, TCF-15, paraxis, protein bHLH-EC2
Species: mouse
Products:     Tcf15

Top Publications

  1. Burgess R, Cserjesi P, Ligon K, Olson E. Paraxis: a basic helix-loop-helix protein expressed in paraxial mesoderm and developing somites. Dev Biol. 1995;168:296-306 pubmed
    ..Here we report the cloning of a bHLH protein, called paraxis, which is nearly identical to scleraxis within the bHLH region but diverges in its amino and carboxyl termini...
  2. Wilson Rawls J, Rhee J, Rawls A. Paraxis is a basic helix-loop-helix protein that positively regulates transcription through binding to specific E-box elements. J Biol Chem. 2004;279:37685-92 pubmed
    ..b>Paraxis is a member of this subfamily, and it has been shown to regulate morphogenetic events during somitogenesis, ..
  3. Burgess R, Rawls A, Brown D, Bradley A, Olson E. Requirement of the paraxis gene for somite formation and musculoskeletal patterning. Nature. 1996;384:570-3 pubmed
    ..b>Paraxis is a basic helix-loop-helix transcription factor expressed in paraxial mesoderm and somites...
  4. Blanar M, Crossley P, Peters K, Steingr msson E, Copeland N, Jenkins N, et al. Meso1, a basic-helix-loop-helix protein involved in mammalian presomitic mesoderm development. Proc Natl Acad Sci U S A. 1995;92:5870-4 pubmed
    ..protein probe for interaction cloning and have isolated a member of the bHLH family of transcription factors, Meso1. Meso1-E2A heterodimers are capable of binding to oligonucleotide probes that contain a bHLH DNA recognition motif...
  5. Bussen M, Petry M, Schuster Gossler K, Leitges M, Gossler A, Kispert A. The T-box transcription factor Tbx18 maintains the separation of anterior and posterior somite compartments. Genes Dev. 2004;18:1209-21 pubmed
    ..In summary, Tbx18 appears to act downstream of Mesp2 and Delta/Notch signaling to maintain the separation of anterior and posterior somite compartments. ..
  6. Hrabe de Angelis M, McIntyre J, Gossler A. Maintenance of somite borders in mice requires the Delta homologue DII1. Nature. 1997;386:717-21 pubmed
  7. Wong P, Zheng H, Chen H, Becher M, Sirinathsinghji D, Trumbauer M, et al. Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 1997;387:288-92 pubmed
    ..Hence, PS1 is required for the spatiotemporal expression of Notch1 and Dll1, which are essential for somite segmentation and maintenance of somite borders. ..
  8. Saga Y, Hata N, Koseki H, Taketo M. Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev. 1997;11:1827-39 pubmed
  9. Casaca A, Nóvoa A, Mallo M. Hoxb6 can interfere with somitogenesis in the posterior embryo through a mechanism independent of its rib-promoting activity. Development. 2016;143:437-48 pubmed publisher
    ..Our results suggest the requirement of precisely regulated Hoxb6 expression for proper segmentation at tailbud stages. ..

More Information


  1. Kokubu C, Heinzmann U, Kokubu T, Sakai N, Kubota T, Kawai M, et al. Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis. Development. 2004;131:5469-80 pubmed
    ..Together, we propose that Lrp6 is one of the key genetic components for the pathogenesis of vertebral segmentation defects and of osteoporosis in humans. ..
  2. Lowe L, Yamada S, Kuehn M. Genetic dissection of nodal function in patterning the mouse embryo. Development. 2001;128:1831-43 pubmed
    ..We find that nodal signaling is required for correct positioning of the anteroposterior axis, normal anterior and midline patterning, and the left-right asymmetric development of the heart, vasculature, lungs and stomach. ..
  3. Johnson J, Rhee J, Parsons S, Brown D, Olson E, Rawls A. The anterior/posterior polarity of somites is disrupted in paraxis-deficient mice. Dev Biol. 2001;229:176-87 pubmed
    ..Here, we report that mice deficient for paraxis, a gene required for somite epithelialization, also display defects in the axial skeleton and peripheral nerves ..
  4. Yoon J, Wold B. The bHLH regulator pMesogenin1 is required for maturation and segmentation of paraxial mesoderm. Genes Dev. 2000;14:3204-14 pubmed
    ..We infer that pMesogenin1 is an essential upstream regulator of trunk paraxial mesoderm development and segmentation. ..
  5. Beckers J, Schlautmann N, Gossler A. The mouse rib-vertebrae mutation disrupts anterior-posterior somite patterning and genetically interacts with a Delta1 null allele. Mech Dev. 2000;95:35-46 pubmed
    ..However, fine genetic mapping places rv into an interval on chromosome seven that does not contain a gene encoding a known component of the Notch signaling pathway. ..
  6. Armand A, Bourajjaj M, Martínez Martínez S, el Azzouzi H, da Costa Martins P, Hatzis P, et al. Cooperative synergy between NFAT and MyoD regulates myogenin expression and myogenesis. J Biol Chem. 2008;283:29004-10 pubmed publisher
    ..Thus, the combined findings provide a novel transcriptional paradigm for the first steps of myogenesis, where a calcineurin/NFATc3 pathway regulates myogenin induction in cooperation with MyoD during myogenesis. ..
  7. Beck Cormier S, Escande M, Souilhol C, Vandormael Pournin S, Sourice S, Pilet P, et al. Notchless is required for axial skeleton formation in mice. PLoS ONE. 2014;9:e98507 pubmed publisher
    ..We also provide evidence that axial defects are due to an increase in apoptotic cell death in the somite at E9.5. These data demonstrate an essential role for Nle1 during organogenesis and in particular during axial development. ..
  8. Seo K, Wang Y, Kokubo H, Kettlewell J, Zarkower D, Johnson R. Targeted disruption of the DM domain containing transcription factor Dmrt2 reveals an essential role in somite patterning. Dev Biol. 2006;290:200-10 pubmed
    ..are alterations in the expression patterns of dermomyotomal and myotomal transcription factors including Pax3, Paraxis, Myf5, myogenin, Mrf4 and MyoD. Despite these defects, embryos harvested from E13...
  9. Kume T, Jiang H, Topczewska J, Hogan B. The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis. Genes Dev. 2001;15:2470-82 pubmed
    ..homozygotes shows that Foxc1 and Foxc2 are both required for transcription in the anterior presomitic mesoderm of paraxis, Mesp1, Mesp2, Hes5, and Notch1, and for the formation of sharp boundaries of Dll1, Lfng, and ephrinB2 expression...
  10. Aulehla A, Wiegraebe W, Baubet V, Wahl M, Deng C, Taketo M, et al. A beta-catenin gradient links the clock and wavefront systems in mouse embryo segmentation. Nat Cell Biol. 2008;10:186-93 pubmed
    ..This gradient of nuclear beta-catenin defines the size of the oscillatory field and controls key aspects of PSM maturation and segment formation, emphasizing the central role of Wnt signalling in this process. ..
  11. Guelman S, Kozuka K, Mao Y, Pham V, Solloway M, Wang J, et al. The double-histone-acetyltransferase complex ATAC is essential for mammalian development. Mol Cell Biol. 2009;29:1176-88 pubmed publisher
  12. Young T, Rowland J, van de Ven C, Bialecka M, Novoa A, Carapuco M, et al. Cdx and Hox genes differentially regulate posterior axial growth in mammalian embryos. Dev Cell. 2009;17:516-26 pubmed publisher
    ..Concomitant regulation of Cyp26a1 expression, restraining retinoic acid signaling away from the posterior growth zone, may likewise play a role in timing the trunk-tail transition. ..
  13. Rowton M, Ramos P, Anderson D, Rhee J, Cunliffe H, Rawls A. Regulation of mesenchymal-to-epithelial transition by PARAXIS during somitogenesis. Dev Dyn. 2013;242:1332-44 pubmed publisher
    ..Somitic MET is initiated in the presomitic mesoderm by PARAXIS-dependent changes in cell adhesion, cell polarity, and the composition of the extracellular matrix...
  14. Dear T, Hainzl T, Follo M, Nehls M, Wilmore H, Matena K, et al. Identification of interaction partners for the basic-helix-loop-helix protein E47. Oncogene. 1997;14:891-8 pubmed
    ..A cDNA encoding part of the nucleolin protein sequence interacted with the E47 basic-helix-loop-helix only when fused to a beta-galactosidase tag. ..
  15. Chawengsaksophak K, de Graaff W, Rossant J, Deschamps J, Beck F. Cdx2 is essential for axial elongation in mouse development. Proc Natl Acad Sci U S A. 2004;101:7641-5 pubmed
    ..The gene appears to be important in the integration of the pathways controlling embryonic axial elongation, and anterior-posterior patterning. ..
  16. Muir T, Wilson Rawls J, Stevens J, Rawls A, Schweitzer R, Kang C, et al. Integration of CREB and bHLH transcriptional signaling pathways through direct heterodimerization of the proteins: role in muscle and testis development. Mol Reprod Dev. 2008;75:1637-52 pubmed publisher
    ..Independent studies of the role of the bHLH protein scleraxis in testicular Sertoli cells and paraxis in muscle development using yeast-2-hybrid screens provided the novel observation that bHLH proteins can directly ..
  17. Bu P, Evrard Y, Lozano G, Dent S. Loss of Gcn5 acetyltransferase activity leads to neural tube closure defects and exencephaly in mouse embryos. Mol Cell Biol. 2007;27:3405-16 pubmed
    ..Together, our results indicate that Gcn5 has important, HAT-independent functions in early development and that Gcn5 acetyltransferase activity is required for cranial neural tube closure in the mouse. ..
  18. Ballow D, Meistrich M, Matzuk M, Rajkovic A. Sohlh1 is essential for spermatogonial differentiation. Dev Biol. 2006;294:161-7 pubmed
    ..Sohlh1 represents the first testis-specific bHLH transcription factor that is essential for spermatogonial differentiation. ..
  19. Ando T, Semba K, Suda H, Sei A, Mizuta H, Araki M, et al. The floor plate is sufficient for development of the sclerotome and spine without the notochord. Mech Dev. 2011;128:129-40 pubmed publisher
  20. Henderson D, Conway S, Copp A. Rib truncations and fusions in the Sp2H mouse reveal a role for Pax3 in specification of the ventro-lateral and posterior parts of the somite. Dev Biol. 1999;209:143-58 pubmed
    ..Our findings point to additional regulatory functions for the Pax3 transcription factor, apart from those already demonstrated for development of the neural tube, neural crest, and dermomyotome. ..
  21. Xu W, Edmondson D, Evrard Y, Wakamiya M, Behringer R, Roth S. Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development. Nat Genet. 2000;26:229-32 pubmed
    ..Our studies are the first to demonstrate that specific acetyltransferases are required for cell survival and mesoderm formation during mammalian development. ..
  22. Melloy P, Ewart J, Cohen M, Desmond M, Kuehn M, Lo C. No turning, a mouse mutation causing left-right and axial patterning defects. Dev Biol. 1998;193:77-89 pubmed
    ..Overall, these findings support the hypothesis that the notochord plays an active role in left/right patterning. Our results suggest that nt may participate in this process by modulating the notochordal expression of HNF-3 beta. ..
  23. Chapman D, Papaioannou V. Three neural tubes in mouse embryos with mutations in the T-box gene Tbx6. Nature. 1998;391:695-7 pubmed
  24. Schwabe G, Trepczik B, Süring K, Brieske N, Tucker A, Sharpe P, et al. Ror2 knockout mouse as a model for the developmental pathology of autosomal recessive Robinow syndrome. Dev Dyn. 2004;229:400-10 pubmed
    ..The Ror2(-/-) mouse provides a suitable model that may help to explain many of the underlying developmental malformations in individuals with Robinow syndrome. ..
  25. Mankoo B, Skuntz S, Harrigan I, Grigorieva E, Candia A, Wright C, et al. The concerted action of Meox homeobox genes is required upstream of genetic pathways essential for the formation, patterning and differentiation of somites. Development. 2003;130:4655-64 pubmed
    ..In particular, our studies place Meox gene function upstream of Pax genes in the regulation of chondrogenic and myogenic differentiation of paraxial mesoderm. ..
  26. Wilson Rawls J, Hurt C, Parsons S, Rawls A. Differential regulation of epaxial and hypaxial muscle development by paraxis. Development. 1999;126:5217-29 pubmed
    ..b>Paraxis is a developmentally regulated transcription factor that is required to direct and maintain the epithelial ..
  27. Biris K, Dunty W, Yamaguchi T. Mouse Ripply2 is downstream of Wnt3a and is dynamically expressed during somitogenesis. Dev Dyn. 2007;236:3167-72 pubmed
    ..Our data are consistent with Ripply2 functioning as a segment boundary determination gene during mammalian embryogenesis. Developmental ..
  28. Phan H, Xu A, Coco C, Srajer G, Wyszomierski S, Evrard Y, et al. GCN5 and p300 share essential functions during early embryogenesis. Dev Dyn. 2005;233:1337-47 pubmed
    ..Our data indicate that p300 cooperates specifically with GCN5 to provide essential functions during early embryogenesis. ..
  29. Chung A, Katz D, Pereira F, Jackson K, DeMayo F, Cooney A, et al. Loss of orphan receptor germ cell nuclear factor function results in ectopic development of the tail bud and a novel posterior truncation. Mol Cell Biol. 2001;21:663-77 pubmed
    ..These results suggest that GCNF regulates a novel and critical developmental pathway involved in normal anteroposterior development. ..
  30. Yasui K, Zhang S, Uemura M, Aizawa S, Ueki T. Expression of a twist-related gene, Bbtwist, during the development of a lancelet species and its relation to cephalochordate anterior structures. Dev Biol. 1998;195:49-59 pubmed
  31. Gregorieff A, Grosschedl R, Clevers H. Hindgut defects and transformation of the gastro-intestinal tract in Tcf4(-/-)/Tcf1(-/-) embryos. EMBO J. 2004;23:1825-33 pubmed
    ..Our results reveal a novel role for Wnt signalling in early gut morphogenesis and suggest that specific Wnt-driven patterning events are determined by the unique tissue distribution of Tcf/Lef family members. ..
  32. Yoon J, Moon R, Wold B. The bHLH class protein pMesogenin1 can specify paraxial mesoderm phenotypes. Dev Biol. 2000;222:376-91 pubmed
    ..Thus, expression patterns of these bHLH genes, together with that of an additional bHLH gene in the mouse, Paraxis, collectively define discrete but highly dynamic prepatterned subdomains of the paraxial mesoderm...
  33. Savory J, Bouchard N, Pierre V, Rijli F, De Repentigny Y, Kothary R, et al. Cdx2 regulation of posterior development through non-Hox targets. Development. 2009;136:4099-110 pubmed publisher
    ..We propose a model wherein Cdx2 functions as an integrator of caudalizing information by coordinating axial elongation and somite patterning through Hox-independent and -dependent pathways, respectively. ..
  34. Davies O, Lin C, Radzisheuskaya A, Zhou X, Taube J, Blin G, et al. Tcf15 primes pluripotent cells for differentiation. Cell Rep. 2013;3:472-84 pubmed publisher
    ..One of these, Tcf15, is also expressed in the embryonic day 4...
  35. Seidl S, Braun U, Roos N, Li S, Lüdtke T, Kispert A, et al. Phenotypical analysis of atypical PKCs in vivo function display a compensatory system at mouse embryonic day 7.5. PLoS ONE. 2013;8:e62756 pubmed publisher
    ..We present a compensatory function of PKC? at E7.5, rescuing the phenotype. Furthermore, this study indicates at least one specific, yet unknown, PKC? function that cannot be compensated by the overexpression of PKC? at E9.5. ..
  36. Bessho Y, Sakata R, Komatsu S, Shiota K, Yamada S, Kageyama R. Dynamic expression and essential functions of Hes7 in somite segmentation. Genes Dev. 2001;15:2642-7 pubmed
    ..These results indicate that Hes7 controls the cyclic expression of lunatic fringe and is essential for coordinated somite segmentation. ..
  37. Ota M, Loebel D, O Rourke M, Wong N, Tsoi B, Tam P. Twist is required for patterning the cranial nerves and maintaining the viability of mesodermal cells. Dev Dyn. 2004;230:216-28 pubmed
  38. Faisst A, Alvarez Bolado G, Treichel D, Gruss P. Rotatin is a novel gene required for axial rotation and left-right specification in mouse embryos. Mech Dev. 2002;113:15-28 pubmed
    ..Our results show a novel key player in the genetic cascade that determines L-R specification, and suggest a causal link between this process and axial rotation. ..
  39. Wang C, Brodnicki T, Copeland N, Jenkins N, Harvey R. Conserved linkage of NK-2 homeobox gene pairs Nkx2-2/2-4 and Nkx2-1/2-9 in mammals. Mamm Genome. 2000;11:466-8 pubmed
  40. Teppner I, Becker S, de Angelis M, Gossler A, Beckers J. Compartmentalised expression of Delta-like 1 in epithelial somites is required for the formation of intervertebral joints. BMC Dev Biol. 2007;7:68 pubmed
    ..Our data suggest that the restricted Dll1 expression in caudal epithelial somites may be particularly required for the proper development of the intervertebral joint forming compartment. ..
  41. Inoue T, Ota M, Mikoshiba K, Aruga J. Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo. Dev Biol. 2007;306:669-84 pubmed
  42. Takahashi Y, Takagi A, Hiraoka S, Koseki H, Kanno J, Rawls A, et al. Transcription factors Mesp2 and Paraxis have critical roles in axial musculoskeletal formation. Dev Dyn. 2007;236:1484-94 pubmed
    Mesp2 and Paraxis are basic helix-loop-helix (bHLH) -type transcription factors coexpressed in the presomitic mesoderm (PSM) and are required for normal somite formation...
  43. Anderson D, Arredondo J, Hahn K, Valente G, Martin J, Wilson Rawls J, et al. Mohawk is a novel homeobox gene expressed in the developing mouse embryo. Dev Dyn. 2006;235:792-801 pubmed
    ..Mohawk transcription in the dorsomedial region required the expression of the transcription factor paraxis. As somites matured, Mohawk transcription was observed in the tendon-specific syndetome and the sclerotome-..
  44. Hidai H, Quertermous E, Espinosa R, LeBeau M, Quertermous T. Genomic organization and chromosomal localization of the gene TCF15 encoding the early mesodermal basic helix-loop-helix factor bHLH-EC2. Genomics. 1995;30:598-601 pubmed
    ..To investigate the possible association of bHLH-EC2 with hematological malignancy, the chromosomal location of this gene in the human was mapped by fluorescence in situ hybridization and assigned to chromosome band 20p13. ..
  45. Petersen P, Tang H, Zou K, Zhong W. The enigma of the numb-Notch relationship during mammalian embryogenesis. Dev Neurosci. 2006;28:156-68 pubmed
    ..We discuss possible mechanisms by which the antagonistic roles of Numb and Notch are evolutionarily conserved to meet the needs of stem cell maintenance during mammalian neurogenesis. ..
  46. McDermott A, Gustafsson M, Elsam T, Hui C, Emerson C, Borycki A. Gli2 and Gli3 have redundant and context-dependent function in skeletal muscle formation. Development. 2005;132:345-57 pubmed
    ..Together, our data demonstrate both positive and negative regulatory functions for Gli2 and Gli3 in the control of Myf5 activation in the epaxial muscle progenitor cells and in dorsoventral and mediolateral patterning of the somite. ..
  47. Lopez T, Fan C. Dynamic CREB family activity drives segmentation and posterior polarity specification in mammalian somitogenesis. Proc Natl Acad Sci U S A. 2013;110:E2019-27 pubmed publisher
    ..Together, these data support that the CREB family acts at the determination front to modulate Wnt signaling and strengthen Notch signaling as a means to orchestrate cells for somite segmentation and anterior/posterior patterning. ..
  48. Koizumi K, Nakajima M, Yuasa S, Saga Y, Sakai T, Kuriyama T, et al. The role of presenilin 1 during somite segmentation. Development. 2001;128:1391-402 pubmed
    ..In summary, we propose that Ps1 is involved in the functional manifestation of the segmentation clock in the presomitic mesoderm. ..
  49. Coppiello G, Collantes M, Sirerol Piquer M, Vandenwijngaert S, Schoors S, Swinnen M, et al. Meox2/Tcf15 heterodimers program the heart capillary endothelium for cardiac fatty acid uptake. Circulation. 2015;131:815-26 pubmed publisher
    ..ECs from heart, brain, and liver, we revealed a genetic signature for microvascular heart ECs and identified Meox2/Tcf15 heterodimers as novel transcriptional determinants...
  50. Zhang L, Levitt R, Kleeberger S. Differential susceptibility to ozone-induced airways hyperreactivity in inbred strains of mice. Exp Lung Res. 1995;21:503-18 pubmed
    ..Pharmacologic studies suggest that although PMNs were associated with O3-induced hyperreactivity, these cells were not the cause of the effect, and that these two events are not codependent. ..
  51. Grainger S, Lam J, Savory J, Mears A, Rijli F, Lohnes D. Cdx regulates Dll1 in multiple lineages. Dev Biol. 2012;361:1-11 pubmed publisher
    ..These findings suggest that Cdx members operate upstream of Dll1 to convey different functions in two distinct lineages. ..
  52. Quertermous E, Hidai H, Blanar M, Quertermous T. Cloning and characterization of a basic helix-loop-helix protein expressed in early mesoderm and the developing somites. Proc Natl Acad Sci U S A. 1994;91:7066-70 pubmed
    ..These findings suggest that bHLH-EC2 plays a role in the development of multiple cell types derived from the primitive mesoderm. ..