Gene Symbol: Hey2
Description: hairy/enhancer-of-split related with YRPW motif 2
Alias: CHF1, Herp1, Hrt2, bHLHb32, hesr2, hairy/enhancer-of-split related with YRPW motif protein 2, HES-related repressor protein 2, HESR-2, HRT-2, Hairy-E(spl)-related with YRPW motif 2, hairy and enhancer of split related 2, hairy and enhancer of split-related protein 2, hairy-related transcription factor 2, mHRT2, protein gridlock homolog
Species: mouse
Products:     Hey2

Top Publications

  1. Chin M, Maemura K, Fukumoto S, Jain M, Layne M, Watanabe M, et al. Cardiovascular basic helix loop helix factor 1, a novel transcriptional repressor expressed preferentially in the developing and adult cardiovascular system. J Biol Chem. 2000;275:6381-7 pubmed
    ..Cardiovascular helix-loop-helix factor 1 (CHF1) is distantly related to the hairy family of transcriptional repressors...
  2. Steidl C, Leimeister C, Klamt B, Maier M, Nanda I, Dixon M, et al. Characterization of the human and mouse HEY1, HEY2, and HEYL genes: cloning, mapping, and mutation screening of a new bHLH gene family. Genomics. 2000;66:195-203 pubmed
    ..bHLH transcription factor genes from mouse and human (hairy and Enhancer-of-split related with YRPW motif; HEY1, HEY2, and HEYL). All three HEY genes have a similar genomic structure with five exons...
  3. Gessler M, Knobeloch K, Helisch A, Amann K, Schumacher N, Rohde E, et al. Mouse gridlock: no aortic coarctation or deficiency, but fatal cardiac defects in Hey2 -/- mice. Curr Biol. 2002;12:1601-4 pubmed
    ..We have generated a knockout of the murine Hey2 (gridlock) gene to analyze the mammalian phenotype...
  4. Donovan J, Kordylewska A, Jan Y, Utset M. Tetralogy of fallot and other congenital heart defects in Hey2 mutant mice. Curr Biol. 2002;12:1605-10 pubmed
    ..Here, we use gene targeting to determine the developmental functions of mouse Hey2, a Hey family member that is expressed during the embryonic development of the heart, arteries, and other organs...
  5. Jalali A, Bassuk A, Kan L, Israsena N, Mukhopadhyay A, McGuire T, et al. HeyL promotes neuronal differentiation of neural progenitor cells. J Neurosci Res. 2011;89:299-309 pubmed publisher
    ..These observations suggest that HeyL promotes neuronal differentiation of neural progenitor cells by activating proneural genes and by inhibiting the actions of other Hes and Hey family members. ..
  6. Xin M, Small E, van Rooij E, Qi X, Richardson J, Srivastava D, et al. Essential roles of the bHLH transcription factor Hrt2 in repression of atrial gene expression and maintenance of postnatal cardiac function. Proc Natl Acad Sci U S A. 2007;104:7975-80 pubmed
    The basic helix-loop-helix transcriptional repressor Hairy-related transcription factor 2 (Hrt2) is expressed in ventricular, but not atrial, cardiomyocytes, and in endothelial and vascular smooth muscle cells...
  7. Koibuchi N, Chin M. CHF1/Hey2 plays a pivotal role in left ventricular maturation through suppression of ectopic atrial gene expression. Circ Res. 2007;100:850-5 pubmed
    We previously reported that mice lacking the hairy-related basic helix-loop-helix (bHLH) transcription factor CHF1/Hey2 develop a thin-walled left ventricle...
  8. Kokubo H, Miyagawa Tomita S, Nakazawa M, Saga Y, Johnson R. Mouse hesr1 and hesr2 genes are redundantly required to mediate Notch signaling in the developing cardiovascular system. Dev Biol. 2005;278:301-9 pubmed
    ..An example of this is evident for mutants of gridlock, the zebrafish counterpart of mouse hesr2, which have vascular defects, whereas mouse hesr2 mutants have only cardiac defects...
  9. Fischer A, Klattig J, Kneitz B, Diez H, Maier M, Holtmann B, et al. Hey basic helix-loop-helix transcription factors are repressors of GATA4 and GATA6 and restrict expression of the GATA target gene ANF in fetal hearts. Mol Cell Biol. 2005;25:8960-70 pubmed
    ..Mice lacking Hey2 develop cardiac hypertrophy, often associated with congenital heart defects, whereas combined Hey1/Hey2 deficiency ..

More Information


  1. Liu Y, Yu M, Wu L, Chin M. The bHLH transcription factor CHF1/Hey2 regulates susceptibility to apoptosis and heart failure after pressure overload. Am J Physiol Heart Circ Physiol. 2010;298:H2082-92 pubmed publisher
    ..factor cardiovascular basic helix-loop-helix factor 1/hairy/enhancer of split related with YRPW motif 2 (CHF1/Hey2) influences the development of cardiac hypertrophy and progression to heart failure under conditions of pressure ..
  2. Iso T, Sartorelli V, Poizat C, Iezzi S, Wu H, Chung G, et al. HERP, a novel heterodimer partner of HES/E(spl) in Notch signaling. Mol Cell Biol. 2001;21:6080-9 pubmed
    b>HERP1 and -2 are members of a new basic helix-loop-helix (bHLH) protein family closely related to HES/E(spl), the only previously known Notch effector...
  3. Xiang F, Sakata Y, Cui L, Youngblood J, Nakagami H, Liao J, et al. Transcription factor CHF1/Hey2 suppresses cardiac hypertrophy through an inhibitory interaction with GATA4. Am J Physiol Heart Circ Physiol. 2006;290:H1997-2006 pubmed
    ..We report the generation of transgenic mice that overexpress the transcription factor CHF1/Hey2 in the myocardium...
  4. Garg V, Muth A, Ransom J, Schluterman M, Barnes R, King I, et al. Mutations in NOTCH1 cause aortic valve disease. Nature. 2005;437:270-4 pubmed
    ..These results suggest that NOTCH1 mutations cause an early developmental defect in the aortic valve and a later de-repression of calcium deposition that causes progressive aortic valve disease. ..
  5. Sakata Y, Kamei C, Nakagami H, Bronson R, Liao J, Chin M. Ventricular septal defect and cardiomyopathy in mice lacking the transcription factor CHF1/Hey2. Proc Natl Acad Sci U S A. 2002;99:16197-202 pubmed
    ..Our results indicate that CHF1 plays an important role in regulation of ventricular septation in mammalian heart development and is important for ..
  6. Seo S, Fujita H, Nakano A, Kang M, Duarte A, Kume T. The forkhead transcription factors, Foxc1 and Foxc2, are required for arterial specification and lymphatic sprouting during vascular development. Dev Biol. 2006;294:458-70 pubmed
    ..Taken together, our results demonstrate that Foxc transcription factors are novel regulators of arterial cell specification upstream of Notch signaling and lymphatic sprouting during embryonic development. ..
  7. Nakagawa O, McFadden D, Nakagawa M, Yanagisawa H, Hu T, Srivastava D, et al. Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling. Proc Natl Acad Sci U S A. 2000;97:13655-60 pubmed
    ..show that the intracellular domain of the Notch1 receptor (Notch1 IC), which is constitutively active, up-regulates HRT2 expression in 10T(1/2) fibroblasts...
  8. Leimeister C, Externbrink A, Klamt B, Gessler M. Hey genes: a novel subfamily of hairy- and Enhancer of split related genes specifically expressed during mouse embryogenesis. Mech Dev. 1999;85:173-7 pubmed
    ..b>Hey2 is similarly expressed in the somites whereas it shows a complementary expression in the heart, the craniofacial ..
  9. Sakata Y, Koibuchi N, Xiang F, Youngblood J, Kamei C, Chin M. The spectrum of cardiovascular anomalies in CHF1/Hey2 deficient mice reveals roles in endocardial cushion, myocardial and vascular maturation. J Mol Cell Cardiol. 2006;40:267-73 pubmed
    CHF1/Hey2 null mice generated in different laboratories have discrepant cardiovascular phenotypes...
  10. Fukada S, Yamaguchi M, Kokubo H, Ogawa R, Uezumi A, Yoneda T, et al. Hesr1 and Hesr3 are essential to generate undifferentiated quiescent satellite cells and to maintain satellite cell numbers. Development. 2011;138:4609-19 pubmed publisher
    ..These results indicate that Hesr1 and Hesr3 are essential for the generation of adult satellite cells and for the maintenance of skeletal muscle homeostasis. ..
  11. Yamamoto N, Chang W, Kelley M. Rbpj regulates development of prosensory cells in the mammalian inner ear. Dev Biol. 2011;353:367-79 pubmed publisher
    ..These results suggest important roles for Rbpj and notch signaling in multiple aspects of inner ear development including prosensory cell maturation, cellular differentiation and survival. ..
  12. Ohyama T, Basch M, Mishina Y, Lyons K, Segil N, Groves A. BMP signaling is necessary for patterning the sensory and nonsensory regions of the developing mammalian cochlea. J Neurosci. 2010;30:15044-51 pubmed publisher
    ..Our results suggest BMP signaling is required for patterning sensory and nonsensory tissue in the mammalian cochlea. ..
  13. Nakagawa O, Nakagawa M, Richardson J, Olson E, Srivastava D. HRT1, HRT2, and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic, and pharyngeal arch segments. Dev Biol. 1999;216:72-84 pubmed
    ..Here, we describe a new subclass of bHLH proteins, HRT1 (Hairy-related transcription factor 1), HRT2, and HRT3, that share high homology with the Hairy family of proteins yet have characteristics that are distinct ..
  14. Doetzlhofer A, Basch M, Ohyama T, Gessler M, Groves A, Segil N. Hey2 regulation by FGF provides a Notch-independent mechanism for maintaining pillar cell fate in the organ of Corti. Dev Cell. 2009;16:58-69 pubmed publisher
    ..not necessary for the differentiation and maintenance of pillar cell fate, that pillar cells are distinguished by Hey2 expression, and that-unlike other Hes/Hey factors-Hey2 expression is Notch independent...
  15. Fischer A, Steidl C, Wagner T, Lang E, Jakob P, Friedl P, et al. Combined loss of Hey1 and HeyL causes congenital heart defects because of impaired epithelial to mesenchymal transition. Circ Res. 2007;100:856-63 pubmed
    ..We further show that loss of Hey2 leads to very similar deficiencies, whereas a Notch1 null mutation completely abolishes epithelial to mesenchymal ..
  16. Fischer A, Schumacher N, Maier M, Sendtner M, Gessler M. The Notch target genes Hey1 and Hey2 are required for embryonic vascular development. Genes Dev. 2004;18:901-11 pubmed
    ..The Hey family of bHLH transcription factors are direct targets of Notch signaling. Loss of Hey2 in the mouse leads to cardiac defects with high postnatal lethality...
  17. Leimeister C, Dale K, Fischer A, Klamt B, Hrabe de Angelis M, Radtke F, et al. Oscillating expression of c-Hey2 in the presomitic mesoderm suggests that the segmentation clock may use combinatorial signaling through multiple interacting bHLH factors. Dev Biol. 2000;227:91-103 pubmed
    ..Furthermore, we analysed the dynamic expression of the respective chicken c-Hey1 and c-Hey2 genes during somitogenesis...
  18. High F, Zhang M, Proweller A, Tu L, Parmacek M, Pear W, et al. An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest. 2007;117:353-63 pubmed
    ..These results provide a molecular and cellular framework for understanding the role of Notch signaling in the etiology of congenital heart disease. ..
  19. Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama K. Fbxw7-dependent degradation of Notch is required for control of "stemness" and neuronal-glial differentiation in neural stem cells. J Biol Chem. 2011;286:13754-64 pubmed publisher
    ..Our results thus implicate Fbxw7 as a key regulator of the maintenance and differentiation of neural stem cells in the brain. ..
  20. Im S, Jeong H, Jeong H, Kim K, Hwang D, Ikegami M, et al. Disruption of sorting nexin 5 causes respiratory failure associated with undifferentiated alveolar epithelial type I cells in mice. PLoS ONE. 2013;8:e58511 pubmed publisher
    ..These results demonstrate that Snx5 is necessary for the differentiation of alveolar epithelial type I cells, which may underlie the adaptation to air breathing at birth...
  21. Iso T, Sartorelli V, Chung G, Shichinohe T, Kedes L, Hamamori Y. HERP, a new primary target of Notch regulated by ligand binding. Mol Cell Biol. 2001;21:6071-9 pubmed
    ..Indeed, a constitutively active NICD indiscriminately up-regulates expression of both HERP1 and HERP2 mRNAs...
  22. Chin S, Romano R, Nagarajan P, Sinha S, Garrett Sinha L. Aberrant epidermal differentiation and disrupted ?Np63/Notch regulatory axis in Ets1 transgenic mice. Biol Open. 2013;2:1336-45 pubmed publisher
    ..Given the established tumor suppressive role for Notch signaling in skin tumorigenesis, the demonstrated ability of Ets1 to interfere with this signaling pathway may be important in mediating its pro-tumorigenic activities. ..
  23. Tsao P, Vasconcelos M, Izvolsky K, Qian J, LU J, Cardoso W. Notch signaling controls the balance of ciliated and secretory cell fates in developing airways. Development. 2009;136:2297-307 pubmed publisher
    ..It might also be relevant to mediate the metaplastic changes in the respiratory epithelium that occur in pathological conditions, such as asthma and chronic obstructive pulmonary disease. ..
  24. Mysliwiec M, Bresnick E, Lee Y. Endothelial Jarid2/Jumonji is required for normal cardiac development and proper Notch1 expression. J Biol Chem. 2011;286:17193-204 pubmed publisher
    ..The identification of Jarid2 as a potential regulator of Notch1 signaling has broad implications for many cellular processes including development, stem cell maintenance, and tumor formation. ..
  25. Tokuzawa Y, Yagi K, Yamashita Y, Nakachi Y, Nikaido I, Bono H, et al. Id4, a new candidate gene for senile osteoporosis, acts as a molecular switch promoting osteoblast differentiation. PLoS Genet. 2010;6:e1001019 pubmed publisher
    ..mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes...
  26. Chen H, Zhang W, Sun X, Yoshimoto M, Chen Z, Zhu W, et al. Fkbp1a controls ventricular myocardium trabeculation and compaction by regulating endocardial Notch1 activity. Development. 2013;140:1946-57 pubmed publisher
    ..Our findings suggest that Fkbp1a-mediated regulation of Notch1 plays an important role in intercellular communication between endocardium and myocardium, which is crucial in controlling the formation of the ventricular walls. ..
  27. Boucherat O, Montaron S, Bérubé Simard F, Aubin J, Philippidou P, Wellik D, et al. Partial functional redundancy between Hoxa5 and Hoxb5 paralog genes during lung morphogenesis. Am J Physiol Lung Cell Mol Physiol. 2013;304:L817-30 pubmed publisher
    ..Altogether, our observations establish that the Hoxa5 and Hoxb5 paralog genes shared some functions during lung morphogenesis, Hoxa5 playing a predominant role. ..
  28. Boukens B, Sylva M, de Gier de Vries C, Remme C, Bezzina C, Christoffels V, et al. Reduced sodium channel function unmasks residual embryonic slow conduction in the adult right ventricular outflow tract. Circ Res. 2013;113:137-41 pubmed publisher
    ..RVOT was characterized by expression of Tbx2, a repressor of differentiation, and absence of expression of both Hey2, a ventricular transcription factor, and Gja1, encoding the principal gap-junction subunit for ventricular fast ..
  29. Kratsios P, Catela C, Salimova E, Huth M, Berno V, Rosenthal N, et al. Distinct roles for cell-autonomous Notch signaling in cardiomyocytes of the embryonic and adult heart. Circ Res. 2010;106:559-72 pubmed publisher
  30. Sakamoto M, Hirata H, Ohtsuka T, Bessho Y, Kageyama R. The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain. J Biol Chem. 2003;278:44808-15 pubmed
    ..Here, we found that the Hes-related basic helix-loop-helix (bHLH) genes Hesr1/Hey1 and Hesr2/Hey2 are expressed in the ventricular zone, which contains neural precursor cells...
  31. Hayashi T, Kokubo H, Hartman B, Ray C, Reh T, Bermingham McDonogh O. Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea. Dev Biol. 2008;316:87-99 pubmed publisher
    ..We report that two members of the Hes-related gene family, Hesr1 and Hesr2, are expressed in the developing cochlea at a time and place that makes them excellent candidates as downstream ..
  32. Benito Gonzalez A, Doetzlhofer A. Hey1 and Hey2 control the spatial and temporal pattern of mammalian auditory hair cell differentiation downstream of Hedgehog signaling. J Neurosci. 2014;34:12865-76 pubmed publisher
    ..Here, we provide evidence that in the murine cochlea, Hey1 and Hey2 control the spatiotemporal pattern of HC differentiation downstream of Hedgehog signaling...
  33. Mukhopadhyay A, Jarrett J, Chlon T, Kessler J. HeyL regulates the number of TrkC neurons in dorsal root ganglia. Dev Biol. 2009;334:142-51 pubmed publisher
    ..Null mutation of HeyL increased expression of the Hey paralogs Hey1 and Hey2, suggesting that HeyL normally inhibits their expression...
  34. Chong D, Koo Y, Xu K, Fu S, Cleaver O. Stepwise arteriovenous fate acquisition during mammalian vasculogenesis. Dev Dyn. 2011;240:2153-65 pubmed publisher
    ..Together, our results provide a first spatiotemporal analysis of mammalian AV cell fate establishment and anatomy, as well as a delineation of a molecular toolkit for analysis of arteries and veins during early vessel development. ..
  35. Heisig J, Weber D, Englberger E, Winkler A, Kneitz S, Sung W, et al. Target gene analysis by microarrays and chromatin immunoprecipitation identifies HEY proteins as highly redundant bHLH repressors. PLoS Genet. 2012;8:e1002728 pubmed publisher
    ..The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target ..
  36. Laforest B, Andelfinger G, Nemer M. Loss of Gata5 in mice leads to bicuspid aortic valve. J Clin Invest. 2011;121:2876-87 pubmed publisher
    ..Mice with mutated Gata5 alleles represent unique models to dissect the mechanisms underlying degenerative aortic valve disease and to develop much-needed preventive and therapeutic interventions. ..
  37. Fischer A, Klamt B, Schumacher N, Glaeser C, Hansmann I, Fenge H, et al. Phenotypic variability in Hey2 -/- mice and absence of HEY2 mutations in patients with congenital heart defects or Alagille syndrome. Mamm Genome. 2004;15:711-6 pubmed
    ..We and others have recently shown that in mice loss of Hey2 results in a high incidence of fatal ventricular and atrial septal defects, combined with tricuspid stenosis or ..
  38. Firulli B, Hadzic D, McDaid J, Firulli A. The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function. J Biol Chem. 2000;275:33567-73 pubmed
    ..Taken together, these results show that dHAND and eHAND can form homo- and heterodimer combinations with multiple bHLH partners and that this broad dimerization profile reflects the mechanisms by which HAND genes regulate transcription. ..
  39. Watanabe T, Koibuchi N, Chin M. Transcription factor CHF1/Hey2 regulates coronary vascular maturation. Mech Dev. 2010;127:418-27 pubmed publisher
    The transcription factor CHF1/Hey2 has been implicated in a variety of cardiovascular developmental abnormalities including ventricular septal defect, deformed valves and cardiomyopathy...
  40. Nomura Kitabayashi A, Anderson G, Sleep G, Mena J, Karabegovic A, Karamath S, et al. Endoglin is dispensable for angiogenesis, but required for endocardial cushion formation in the midgestation mouse embryo. Dev Biol. 2009;335:66-77 pubmed publisher
  41. 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. ..
  42. Guo M, Zhang H, Bian F, Li G, Mu X, Wen J, et al. P4 down-regulates Jagged2 and Notch1 expression during primordial folliculogenesis. Front Biosci (Elite Ed). 2012;4:2631-44 pubmed
    ..In the present study, transcript levels of Jagged2, Notch1, and their target, Hey2, increased markedly in ovaries during the beginning stage of folliculogenesis (17...
  43. Robert Moreno A, Espinosa L, de la Pompa J, Bigas A. RBPjkappa-dependent Notch function regulates Gata2 and is essential for the formation of intra-embryonic hematopoietic cells. Development. 2005;132:1117-26 pubmed
    ..Taken together, these data strongly suggest that activation of Gata2 expression by Notch1/RBPjkappa is a crucial event for the onset of definitive hematopoiesis in the embryo. ..
  44. Plageman T, Yutzey K. Microarray analysis of Tbx5-induced genes expressed in the developing heart. Dev Dyn. 2006;235:2868-80 pubmed
    ..These genes represent new candidate gene targets of Tbx5 that may be related to congenital heart malformations associated with HOS. ..
  45. Park J, Raafat A, Feltracco J, Blanding W, Booth B. Differential gene expression in nuclear label-retaining cells in the developing mouse mammary gland. Stem Cells Dev. 2013;22:1297-306 pubmed publisher
    ..Expression of Notch-inducible genes, Hes1 and Hey2, was elevated in LRCs...
  46. Lee S, Lee S, Yang H, Song S, Kim K, Saunders T, et al. Notch pathway targets proangiogenic regulator Sox17 to restrict angiogenesis. Circ Res. 2014;115:215-26 pubmed publisher
    ..Our findings demonstrate that the Notch pathway restricts sprouting angiogenesis by reducing the expression of proangiogenic regulator Sox17. ..
  47. Tang Y, Urs S, Liaw L. Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by interfering with Notch intracellular domain/CBF-1 complex interaction with the CBF-1-binding site. Circ Res. 2008;102:661-8 pubmed publisher
    ..NotchICD also induce expression of the transcriptional repressors HRT1 (Hairy-related transcription factor 1) and HRT2, in a CBF-1-dependent manner...
  48. Jia J, Lin M, Zhang L, York J, Zhang P. The Notch signaling pathway controls the size of the ocular lens by directly suppressing p57Kip2 expression. Mol Cell Biol. 2007;27:7236-47 pubmed
    ..We found that the Notch effector Herp2 is expressed in lens epithelium and directly suppresses p57Kip2 expression, providing a molecular link between Notch signaling and the cell cycle control machinery during lens development. ..
  49. Nichol D, Shawber C, Fitch M, Bambino K, Sharma A, Kitajewski J, et al. Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7. Blood. 2010;116:6133-43 pubmed publisher
    ..In conclusion, we have uncovered a critical role for Egfl7 in vascular development and have shown that some of these functions are mediated through modulation of Notch signaling. ..
  50. Kokubo H, Tomita Miyagawa S, Hamada Y, Saga Y. Hesr1 and Hesr2 regulate atrioventricular boundary formation in the developing heart through the repression of Tbx2. Development. 2007;134:747-55 pubmed
    ..Hesr1 (Hey1) and Hesr2 (Hey2) are specifically expressed in the atrium and ventricle, respectively, implicating these genes in chamber ..
  51. Tateya T, Sakamoto S, Imayoshi I, Kageyama R. In vivo overactivation of the Notch signaling pathway in the developing cochlear epithelium. Hear Res. 2015;327:209-17 pubmed publisher
    ..Thus, an appropriate level of Notch signaling is needed for the normal extension of the cochlear epithelium and for differentiation of both hair cells and supporting cells. ..
  52. Hartman M, Liu Y, Zhu W, Chien W, Weldy C, Fishman G, et al. Myocardial deletion of transcription factor CHF1/Hey2 results in altered myocyte action potential and mild conduction system expansion but does not alter conduction system function or promote spontaneous arrhythmias. FASEB J. 2014;28:3007-15 pubmed publisher
    b>CHF1/Hey2 is a Notch-responsive basic helix-loop-helix transcription factor involved in cardiac development. Common variants in Hey2 are associated with Brugada syndrome...
  53. Mansour S, Li C, Urness L. Genetic rescue of Muenke syndrome model hearing loss reveals prolonged FGF-dependent plasticity in cochlear supporting cell fates. Genes Dev. 2013;27:2320-31 pubmed publisher
    ..This property might be exploited for the regulation of sensory cell regeneration from support cells. ..
  54. Black B. A single mutation causes a spectrum of cardiovascular defects: the potential role of genetic modifiers, epigenetic influences, and stochastic events in phenotypic variability. J Mol Cell Cardiol. 2006;40:201-4 pubmed
  55. Quintes S, Brinkmann B, Ebert M, Fröb F, Kungl T, Arlt F, et al. Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair. Nat Neurosci. 2016;19:1050-1059 pubmed publisher
    ..However, nerve regeneration and remyelination are both perturbed, demonstrating that Zeb2, although undetectable in adult Schwann cells, has a latent function throughout life. ..
  56. Mommersteeg M, Yeh M, Parnavelas J, Andrews W. Disrupted Slit-Robo signalling results in membranous ventricular septum defects and bicuspid aortic valves. Cardiovasc Res. 2015;106:55-66 pubmed publisher
  57. Iso T, Chung G, Hamamori Y, Kedes L. HERP1 is a cell type-specific primary target of Notch. J Biol Chem. 2002;277:6598-607 pubmed
    ..However, expression of another member of the HERP family, HERP1, was not induced by ligand stimulation in any cells tested, leading to the suggestion that HERP1 may not be an ..
  58. Corada M, Nyqvist D, Orsenigo F, Caprini A, Giampietro C, Taketo M, et al. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell. 2010;18:938-49 pubmed publisher
    ..We propose that early and sustained beta-catenin signaling prevents correct endothelial cell differentiation, altering vascular remodeling and arteriovenous specification. ..
  59. Wu S, Cheng C, Lanz R, Wang T, Respress J, Ather S, et al. Atrial identity is determined by a COUP-TFII regulatory network. Dev Cell. 2013;25:417-26 pubmed publisher
    ..Chromatin immunoprecipitation assays using E13.5 atria identified classic atrial-ventricular identity genes Tbx5, Hey2, Irx4, MLC2v, MLC2a, and MLC1a, among many other cardiac genes, as potential COUP-TFII direct targets...
  60. Nakatani T, Mizuhara E, Minaki Y, Sakamoto Y, Ono Y. Helt, a novel basic-helix-loop-helix transcriptional repressor expressed in the developing central nervous system. J Biol Chem. 2004;279:16356-67 pubmed
    ..Helt could homodimerize, and heterodimerize with Hes5 or Hey2. Both the bHLH and Orange domains were involved in the homodimerization...
  61. Li J, Miao L, Shieh D, Spiotto E, Li J, Zhou B, et al. Single-Cell Lineage Tracing Reveals that Oriented Cell Division Contributes to Trabecular Morphogenesis and Regional Specification. Cell Rep. 2016;15:158-170 pubmed publisher
    ..Furthermore, N-Cadherin deletion in labeled clones disrupted the clonal patterns. In summary, our data demonstrate that OCD contributes to trabecular morphogenesis and specification. ..
  62. Tateya T, Imayoshi I, Tateya I, Hamaguchi K, Torii H, Ito J, et al. Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea. Development. 2013;140:3848-57 pubmed publisher
  63. Yang J, Bücker S, Jungblut B, Böttger T, Cinnamon Y, Tchorz J, et al. Inhibition of Notch2 by Numb/Numblike controls myocardial compaction in the heart. Cardiovasc Res. 2012;96:276-85 pubmed publisher
    ..This study identified potential novel roles of Numb/Numblike in regulating trabeculation and compaction by inhibiting Notch2 and Bmp10 signalling. ..
  64. Kanno K, Ishiura S. Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats. J Neurosci Res. 2011;89:562-75 pubmed publisher
    ..Other members of the HESR (HEY) family, including HESR2 (HEY2) and 3 (HEYL), have similar DNA-binding domains...
  65. Goldberg L, Aujla P, Raetzman L. Persistent expression of activated Notch inhibits corticotrope and melanotrope differentiation and results in dysfunction of the HPA axis. Dev Biol. 2011;358:23-32 pubmed publisher
    ..Taken together, these findings show that Notch signaling is sufficient to prevent corticotrope and melanotrope differentiation, resulting in dysregulation of the HPA axis. ..
  66. Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, et al. Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem. 2004;279:9417-23 pubmed
    ..Expression of Notch1, -2, or -3 or of cyclin E was unaffected in Fbw7(-/-) embryos. Mammalian Fbw7 thus appears to play an indispensable role in negative regulation of the Notch4-Hey1 pathway and is required for vascular development. ..
  67. Zanotti S, Canalis E. Hairy and Enhancer of Split-related with YRPW motif (HEY)2 regulates bone remodeling in mice. J Biol Chem. 2013;288:21547-57 pubmed publisher
    Notch induces Hairy and Enhancer of Split-related with YRPW motif (Hey)1, Hey2, and HeyL expression in osteoblasts, but the contributions of these genes to the skeletal effects of Notch are not fully understood...
  68. Maier M, Gessler M. Comparative analysis of the human and mouse Hey1 promoter: Hey genes are new Notch target genes. Biochem Biophys Res Commun. 2000;275:652-60 pubmed
    Hey genes (Hey1, Hey2 and HeyL) encode a new group of basic helix-loop-helix transcription factors that are related to the hairy/Enhancer of split genes...
  69. Zhu Q, Kim Y, Wang D, Oh S, Luo K. SnoN facilitates ALK1-Smad1/5 signaling during embryonic angiogenesis. J Cell Biol. 2013;202:937-50 pubmed publisher
    ..5. Thus, SnoN is essential for TGF-?/BMP9-dependent biological processes by its ability to both positively and negatively modulate the activities of Smad-dependent pathways. ..
  70. Vincentz J, Firulli B, Lin A, Spicer D, Howard M, Firulli A. Twist1 controls a cell-specification switch governing cell fate decisions within the cardiac neural crest. PLoS Genet. 2013;9:e1003405 pubmed publisher
    ..These data demonstrate that Twist1 functions in post-migratory neural crest cells to repress pro-neural factors and thereby regulate cell fate determination between ectodermal and mesodermal lineages. ..
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