Hes1

Summary

Gene Symbol: Hes1
Description: hes family bHLH transcription factor 1
Alias: Hry, bHLHb39, transcription factor HES-1, hairy and enhancer of split 1
Species: mouse
Products:     Hes1

Top Publications

  1. Ohtsuka T, Imayoshi I, Shimojo H, Nishi E, Kageyama R, McConnell S. Visualization of embryonic neural stem cells using Hes promoters in transgenic mice. Mol Cell Neurosci. 2006;31:109-22 pubmed
    ..Our results suggest that pHes-EGFP transgenic mice can be used to explore similarities and differences among neural stem cells during development. ..
  2. Kita A, Imayoshi I, Hojo M, Kitagawa M, Kokubu H, Ohsawa R, et al. Hes1 and Hes5 control the progenitor pool, intermediate lobe specification, and posterior lobe formation in the pituitary development. Mol Endocrinol. 2007;21:1458-66 pubmed
    ..Here, we report that mice deficient for Hes1 and Hes5 display severe pituitary hypoplasia caused by accelerated differentiation of progenitor cells...
  3. Morimoto M, Liu Z, Cheng H, Winters N, Bader D, Kopan R. Canonical Notch signaling in the developing lung is required for determination of arterial smooth muscle cells and selection of Clara versus ciliated cell fate. J Cell Sci. 2010;123:213-24 pubmed publisher
    ..Unexpectedly, and in contrast to Pofut1-null epithelium, Hes1 expression was only marginally reduced in RBPjkappa-null epithelium, with a corresponding minimal effect on ..
  4. Kopinke D, Brailsford M, Shea J, Leavitt R, Scaife C, Murtaugh L. Lineage tracing reveals the dynamic contribution of Hes1+ cells to the developing and adult pancreas. Development. 2011;138:431-41 pubmed publisher
    ..In the embryonic pancreas, Notch and its target gene Hes1 are thought to inhibit endocrine and exocrine specification...
  5. Brown N, Kanekar S, Vetter M, Tucker P, Gemza D, Glaser T. Math5 encodes a murine basic helix-loop-helix transcription factor expressed during early stages of retinal neurogenesis. Development. 1998;125:4821-33 pubmed
    ..To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos...
  6. Cau E, Casarosa S, Guillemot F. Mash1 and Ngn1 control distinct steps of determination and differentiation in the olfactory sensory neuron lineage. Development. 2002;129:1871-80 pubmed
    ..These results illustrate the versatility of neural bHLH genes which adopt either a determination or a differentiation function, depending primarily on the timing of their expression in neural progenitors. ..
  7. Lee H, Wroblewski E, Philips G, Stair C, Conley K, Reedy M, et al. Multiple requirements for Hes 1 during early eye formation. Dev Biol. 2005;284:464-78 pubmed
    During embryogenesis, multiple developmental processes are integrated through their precise temporal regulation. Hes1 is a transcriptional repressor that regulates the timing of mammalian retinal neurogenesis...
  8. Kageyama R, Niwa Y, Shimojo H. Rhythmic gene expression in somite formation and neural development. Mol Cells. 2009;27:497-502 pubmed publisher
    ..Expression of a related gene, Hes1, also oscillates by negative feedback with a period of about two hours in many cell types such as neural progenitor ..
  9. Wendorff A, Koch U, Wunderlich F, Wirth S, Dubey C, Bruning J, et al. Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation. Immunity. 2010;33:671-84 pubmed publisher
    ..We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell ..

More Information

Publications79

  1. Sanalkumar R, Indulekha C, Divya T, Divya M, Anto R, Vinod B, et al. ATF2 maintains a subset of neural progenitors through CBF1/Notch independent Hes-1 expression and synergistically activates the expression of Hes-1 in Notch-dependent neural progenitors. J Neurochem. 2010;113:807-18 pubmed publisher
  2. Kobayashi T, Kageyama R. Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling. Genes Cells. 2010;15:689-98 pubmed publisher
    ..Recent analysis has shown that Hes1 expression oscillates with a period of about 3-5 h in mouse ES cells and that this oscillating expression ..
  3. Prozorovski T, Schulze Topphoff U, Glumm R, Baumgart J, Schröter F, Ninnemann O, et al. Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol. 2008;10:385-94 pubmed publisher
    ..Under oxidative conditions in vitro and in vivo, Sirt1 was upregulated in NPCs, bound to the transcription factor Hes1 and subsequently inhibited pro-neuronal Mash1...
  4. Kopinke D, Brailsford M, Pan F, Magnuson M, Wright C, Murtaugh L. Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreas. Dev Biol. 2012;362:57-64 pubmed publisher
    ..We previously developed mice in which cells expressing the Notch target gene Hes1 can be labeled and manipulated, by expression of Cre recombinase, and demonstrated that Hes1(+) CACs do not behave ..
  5. Sumazaki R, Shiojiri N, Isoyama S, Masu M, Keino Masu K, Osawa M, et al. Conversion of biliary system to pancreatic tissue in Hes1-deficient mice. Nat Genet. 2004;36:83-7 pubmed
    ..The molecular mechanisms that determine the identity of each organ in this complex area are unknown. Hes1 encodes the basic helix-loop-helix protein Hes1 (ref...
  6. Lütolf S, Radtke F, Aguet M, Suter U, Taylor V. Notch1 is required for neuronal and glial differentiation in the cerebellum. Development. 2002;129:373-85 pubmed
    ..We have also analyzed the effects of Notch1 ablation on gliogenesis in vivo. Our results show that Notch1 is required for both neuron and glia formation and modulates the onset of neurogenesis within the cerebellar neuroepithelium. ..
  7. Bai G, Sheng N, Xie Z, Bian W, Yokota Y, Benezra R, et al. Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1. Dev Cell. 2007;13:283-97 pubmed
    Negative bHLH transcription factor Hes1 can inhibit neural stem cells (NSCs) from precocious neurogenesis through repressing proneural gene expression; therefore, sustenance of Hes1 expression is crucial for NSC pool maintenance...
  8. Kobayashi T, Mizuno H, Imayoshi I, Furusawa C, Shirahige K, Kageyama R. The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells. Genes Dev. 2009;23:1870-5 pubmed publisher
    ..Here, we found that expression of Hes1 and its downstream genes oscillate in mouse embryonic stem (ES) cells...
  9. Tomita K, Ishibashi M, Nakahara K, Ang S, Nakanishi S, Guillemot F, et al. Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis. Neuron. 1996;16:723-34 pubmed
    Mammalian hairy and Enhancer of split homolog 1 (HES1), a basic helix-loop-helix factor gene, is expressed in retinal progenitor cells, and its expression decreases as differentiation proceeds...
  10. Apelqvist A, Li H, Sommer L, Beatus P, Anderson D, Honjo T, et al. Notch signalling controls pancreatic cell differentiation. Nature. 1999;400:877-81 pubmed
    ..These data provide evidence that ngn3 acts as proendocrine gene and that Notch signalling is critical for the decision between the endocrine and progenitor/exocrine fates in the developing pancreas. ..
  11. Hamada Y, Kadokawa Y, Okabe M, Ikawa M, Coleman J, Tsujimoto Y. Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development. 1999;126:3415-24 pubmed
    ..The results indicate that Notch2 plays an essential role in postimplantation development in mice, probably in some aspect of cell specification and/or differentiation, and that the ankyrin repeats are indispensable for its function. ..
  12. Ma L, Cantrup R, Varrault A, Colak D, Klenin N, Gotz M, et al. Zac1 functions through TGFbetaII to negatively regulate cell number in the developing retina. Neural Dev. 2007;2:11 pubmed
    ..This raises the intriguing possibility that tumorigenicity may also be associated with the loss of feedback inhibition in mature tissues. ..
  13. Robert Moreno A, Guiu J, Ruiz Herguido C, López M, Inglés Esteve J, Riera L, et al. Impaired embryonic haematopoiesis yet normal arterial development in the absence of the Notch ligand Jagged1. EMBO J. 2008;27:1886-95 pubmed publisher
    ..Taken together, our results indicate that Jagged1-mediated activation of Notch1 is responsible for regulating GATA2 expression in the AGM, which in turn is essential for definitive haematopoiesis in the mouse. ..
  14. Yoshiura S, Ohtsuka T, Takenaka Y, Nagahara H, Yoshikawa K, Kageyama R. Ultradian oscillations of Stat, Smad, and Hes1 expression in response to serum. Proc Natl Acad Sci U S A. 2007;104:11292-7 pubmed
    ..Although expression of many genes is up- or down-regulated after serum stimulation, the Notch effector Hes1 displays oscillatory response...
  15. Kopp J, Dubois C, Schaffer A, Hao E, Shih H, Seymour P, et al. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development. 2011;138:653-65 pubmed publisher
  16. Randall V, McCue K, Roberts C, Kyriakopoulou V, Beddow S, Barrett A, et al. Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice. J Clin Invest. 2009;119:3301-10 pubmed publisher
    ..We could not rescue PAA morphogenesis by restoring neural crest Chd7 expression. Rather, biallelic expression of Chd7 and Tbx1 in the pharyngeal ectoderm was required for normal PAA development...
  17. Nakayama K, Satoh T, Igari A, Kageyama R, Nishida E. FGF induces oscillations of Hes1 expression and Ras/ERK activation. Curr Biol. 2008;18:R332-4 pubmed publisher
  18. Ong C, Cheng H, Chang L, Ohtsuka T, Kageyama R, Stormo G, et al. Target selectivity of vertebrate notch proteins. Collaboration between discrete domains and CSL-binding site architecture determines activation probability. J Biol Chem. 2006;281:5106-19 pubmed
    ..Consistent with the prediction that "preferred" targets (Hes1) should respond faster and at lower Notch concentration than other targets, we showed that Hes5-GFP was ..
  19. 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. ..
  20. Hald J, Hjorth J, German M, Madsen O, Serup P, Jensen J. Activated Notch1 prevents differentiation of pancreatic acinar cells and attenuate endocrine development. Dev Biol. 2003;260:426-37 pubmed
  21. Shih H, Kopp J, Sandhu M, Dubois C, Seymour P, Grapin Botton A, et al. A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation. Development. 2012;139:2488-99 pubmed publisher
    ..at high Notch activity endocrine differentiation is blocked, as Notch also induces expression of the Ngn3 repressor Hes1. At the transition from high to intermediate Notch activity, only Sox9, but not Hes1, is maintained, thus de-..
  22. Takatsuka K, Hatakeyama J, Bessho Y, Kageyama R. Roles of the bHLH gene Hes1 in retinal morphogenesis. Brain Res. 2004;1004:148-55 pubmed
    ..Previously, we demonstrated that the bHLH gene Hes1 inhibits neuronal differentiation whereas, in Hes1-null retina, precursors prematurely differentiate into neurons ..
  23. Kamakura S, Oishi K, Yoshimatsu T, Nakafuku M, Masuyama N, Gotoh Y. Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling. Nat Cell Biol. 2004;6:547-54 pubmed
    ..Here we show that STAT3 is activated in the presence of active Notch, as well as the Notch effectors Hes1 and Hes5...
  24. Ichi S, Costa F, Bischof J, Nakazaki H, Shen Y, Boshnjaku V, et al. Folic acid remodels chromatin on Hes1 and Neurog2 promoters during caudal neural tube development. J Biol Chem. 2010;285:36922-32 pubmed publisher
    ..Using tissue from caudal neural tubes of murine embryos we also examined H3K27me2 and KDM6B association with Hes1 and Neurog2 promoters at embryonic day E10.5, the proliferative stage, and E12...
  25. Imayoshi I, Isomura A, Harima Y, Kawaguchi K, Kori H, Miyachi H, et al. Oscillatory control of factors determining multipotency and fate in mouse neural progenitors. Science. 2013;342:1203-8 pubmed publisher
    The basic helix-loop-helix transcription factors Ascl1/Mash1, Hes1, and Olig2 regulate fate choice of neurons, astrocytes, and oligodendrocytes, respectively. These same factors are coexpressed by neural progenitor cells...
  26. Ju B, Solum D, Song E, Lee K, Rose D, Glass C, et al. Activating the PARP-1 sensor component of the groucho/ TLE1 corepressor complex mediates a CaMKinase IIdelta-dependent neurogenic gene activation pathway. Cell. 2004;119:815-29 pubmed
    ..Here we report a pathway in which induction of CaMKIIdelta triggers an unexpected switch in the function of the HES1 transcription factor from a TLE-dependent repressor to an activator required for neuronal differentiation...
  27. Hirata H, Yoshiura S, Ohtsuka T, Bessho Y, Harada T, Yoshikawa K, et al. Oscillatory expression of the bHLH factor Hes1 regulated by a negative feedback loop. Science. 2002;298:840-3 pubmed
    ..that serum treatment of cultured cells induces cyclic expression of both mRNA and protein of the Notch effector Hes1, a basic helix-loop-helix (bHLH) factor, with 2-hour periodicity...
  28. Hasegawa K, Okamura Y, Saga Y. Notch signaling in Sertoli cells regulates cyclical gene expression of Hes1 but is dispensable for mouse spermatogenesis. Mol Cell Biol. 2012;32:206-15 pubmed publisher
    ..Caenorhabditis elegans, is cyclically activated in Sertoli cells and regulates stage-dependent gene expression of Hes1. To elucidate the regulatory mechanism of stage-dependent Hes1 expression and the role of Notch signaling in mouse ..
  29. Ito T, Udaka N, Yazawa T, Okudela K, Hayashi H, Sudo T, et al. Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium. Development. 2000;127:3913-21 pubmed
    ..homologs of achaete-scute complex (Mash1) (Ascl1 - Mouse Genome Informatics); hairy and enhancer of split1 (Hes1); and the expression of Notch/Notch-ligand system in the fetal and adult mouse lungs, and in the lungs of Mash1- or ..
  30. Zine A, Aubert A, Qiu J, Therianos S, Guillemot F, Kageyama R, et al. Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear. J Neurosci. 2001;21:4712-20 pubmed
    ..The basic helix-loop-helix (bHLH) genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologs) can influence cell fate determination by acting as ..
  31. Aguilera C, Hoya Arias R, Haegeman G, Espinosa L, Bigas A. Recruitment of IkappaBalpha to the hes1 promoter is associated with transcriptional repression. Proc Natl Acad Sci U S A. 2004;101:16537-42 pubmed
    ..experiments demonstrate that IkappaBalpha is recruited to the promoter regions of the Notch-target gene, hes1, together with HDAC1 and -5, whereas we did not detect IkappaBalpha associated with classical NF-kappaB target ..
  32. Esni F, Ghosh B, Biankin A, Lin J, Albert M, Yu X, et al. Notch inhibits Ptf1 function and acinar cell differentiation in developing mouse and zebrafish pancreas. Development. 2004;131:4213-24 pubmed
    ..In developing mouse pancreas, the Notch target gene Hes1 is co-expressed with Ptf1-P48 in exocrine precursor cells, but not in differentiated amylase-positive acinar cells...
  33. Raetzman L, Cai J, Camper S. Hes1 is required for pituitary growth and melanotrope specification. Dev Biol. 2007;304:455-66 pubmed
    ..precursor cells express many members of the Notch signaling pathway including the downstream effector gene Hes1. We hypothesized that Hes1 regulates the timing of precursor differentiation and cell fate determination...
  34. Wang Y, Dakubo G, Thurig S, Mazerolle C, Wallace V. Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina. Development. 2005;132:5103-13 pubmed
    ..These changes were correlated with the downregulation of cyclin D1 and Hes1 gene expression...
  35. Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F, Kageyama R. Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J. 1999;18:2196-207 pubmed
    ..To understand the intracellular pathway of mammalian Notch, the role of the bHLH genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologues) was examined by retrovirally misexpressing the ..
  36. Georgia S, Soliz R, Li M, Zhang P, Bhushan A. p57 and Hes1 coordinate cell cycle exit with self-renewal of pancreatic progenitors. Dev Biol. 2006;298:22-31 pubmed
    ..We report that p57 is a direct target of transcriptional repression by Notch effector, Hes1. Inactivation of Hes1 results in the upregulation of p57 expression in progenitors, leading to cell cycle arrest, ..
  37. Wall D, Mears A, McNeill B, Mazerolle C, Thurig S, Wang Y, et al. Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity. J Cell Biol. 2009;184:101-12 pubmed publisher
    ..Here, we investigate the link between the Shh signaling pathway and Hes1, a classical Notch target...
  38. Murata K, Hattori M, Hirai N, Shinozuka Y, Hirata H, Kageyama R, et al. Hes1 directly controls cell proliferation through the transcriptional repression of p27Kip1. Mol Cell Biol. 2005;25:4262-71 pubmed
    A transcriptional regulator, Hes1, plays crucial roles in the control of differentiation and proliferation of neuronal, endocrine, and T-lymphocyte progenitors during development...
  39. Rowan S, Conley K, Le T, Donner A, Maas R, Brown N. Notch signaling regulates growth and differentiation in the mammalian lens. Dev Biol. 2008;321:111-22 pubmed publisher
    ..Our data suggest both Cyclin D1 and Cyclin D2, and the p27(Kip1) cyclin-dependent kinase inhibitor act downstream of Notch signaling, and define multiple critical functions for this pathway during lens development. ..
  40. Guseh J, Bores S, Stanger B, Zhou Q, Anderson W, Melton D, et al. Notch signaling promotes airway mucous metaplasia and inhibits alveolar development. Development. 2009;136:1751-9 pubmed publisher
    ..Occasional distal cystic cells appeared to differentiate into normal proximal airway cells, suggesting that ectopic Notch signaling arrests the normal differentiation of distal lung progenitors before they initiate an alveolar program. ..
  41. Bae S, Bessho Y, Hojo M, Kageyama R. The bHLH gene Hes6, an inhibitor of Hes1, promotes neuronal differentiation. Development. 2000;127:2933-43 pubmed
    ..Hes6 is expressed by both undifferentiated and differentiated cells, unlike Hes1, which is expressed only by the former cells...
  42. 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. ..
  43. Fukuda A, Kawaguchi Y, Furuyama K, Kodama S, Horiguchi M, Kuhara T, et al. Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas. J Clin Invest. 2006;116:1484-93 pubmed
    Ectopic pancreas is a developmental anomaly occasionally found in humans. Hes1, a main effector of Notch signaling, regulates the fate and differentiation of many cell types during development...
  44. Shimojo H, Ohtsuka T, Kageyama R. Oscillations in notch signaling regulate maintenance of neural progenitors. Neuron. 2008;58:52-64 pubmed publisher
    Expression of the Notch effector gene Hes1 is required for maintenance of neural progenitors in the embryonic brain, but persistent and high levels of Hes1 expression inhibit proliferation and differentiation of these cells...
  45. Hatakeyama J, Bessho Y, Katoh K, Ookawara S, Fujioka M, Guillemot F, et al. Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development. 2004;131:5539-50 pubmed
    ..Here, we report that inactivation of Hes1 and Hes5, known Notch effectors, and additional inactivation of Hes3 extensively accelerate cell differentiation ..
  46. Jouve C, Palmeirim I, Henrique D, Beckers J, Gossler A, Ish Horowicz D, et al. Notch signalling is required for cyclic expression of the hairy-like gene HES1 in the presomitic mesoderm. Development. 2000;127:1421-9 pubmed
    ..hairy-related gene, c-hairy2, which also cycles in the PSM and whose sequence is closely related to the mammalian HES1 gene, a downstream target of Notch signalling in vertebrates...
  47. Moriyama M, Osawa M, Mak S, Ohtsuka T, Yamamoto N, Han H, et al. Notch signaling via Hes1 transcription factor maintains survival of melanoblasts and melanocyte stem cells. J Cell Biol. 2006;173:333-9 pubmed
    ..The defect is caused by a dramatic elimination of Mbs and MSCs. Furthermore, targeted overexpression of Hes1 is sufficient to protect Mbs from the elimination by apoptosis...
  48. Rochais F, Dandonneau M, Mesbah K, Jarry T, Mattei M, Kelly R. Hes1 is expressed in the second heart field and is required for outflow tract development. PLoS ONE. 2009;4:e6267 pubmed publisher
    ..Here we show that the integration site of the A17-Myf5-nlacZ-T55 transgene lies upstream of Hes1, encoding a basic helix-loop-helix containing transcriptional repressor required for the maintenance of diverse ..
  49. Zheng J, Shou J, Guillemot F, Kageyama R, Gao W. Hes1 is a negative regulator of inner ear hair cell differentiation. Development. 2000;127:4551-60 pubmed
    ..To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis...
  50. Horn S, Kobberup S, Jørgensen M, Kalisz M, Klein T, Kageyama R, et al. Mind bomb 1 is required for pancreatic ?-cell formation. Proc Natl Acad Sci U S A. 2012;109:7356-61 pubmed publisher
    ..distorted P-D patterning and suppressed ?-cell formation, as did conditional inactivation of the Notch target gene Hes1. Our results reveal iterative use of Notch in pancreatic development to ensure correct P-D patterning and adequate ?..
  51. Kawamata S, Du C, Li K, Lavau C. Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations. Oncogene. 2002;21:3855-63 pubmed
    ..Hes-transplanted mice remained healthy but cells transduced with Hes1 or Hes5 were partially impaired in their ability to differentiate into B cells...
  52. Harmon E, Apelqvist A, Smart N, Gu X, Osborne D, Kim S. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Development. 2004;131:6163-74 pubmed
    ..Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development. ..
  53. Seta Y, Seta C, Barlow L. Notch-associated gene expression in embryonic and adult taste papillae and taste buds suggests a role in taste cell lineage decisions. J Comp Neurol. 2003;464:49-61 pubmed
    ..Notch receptors, their ligands, Delta-like 1 (Dll-1), Jagged1, and Jagged2, as well as three transcription factors, Hes1, Hes6, and Mash1, are expressed in the embryonic taste epithelium...
  54. 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. ..
  55. Ishibashi M, Moriyoshi K, Sasai Y, Shiota K, Nakanishi S, Kageyama R. Persistent expression of helix-loop-helix factor HES-1 prevents mammalian neural differentiation in the central nervous system. EMBO J. 1994;13:1799-805 pubmed
    ..A HES-1 and lacZ-transducing retrovirus (SG-HES1) and a control lacZ-transducing retrovirus (SG) were injected into the lateral ventricles of mouse embryos, and the ..
  56. Sasai Y, Kageyama R, Tagawa Y, Shigemoto R, Nakanishi S. Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split. Genes Dev. 1992;6:2620-34 pubmed
    ..These results suggest that HES-1 may play an important role in mammalian development by negatively acting on the two different sequences while HES-3 acts as a repressor in a specific type of neurons. ..
  57. Nelson B, Hartman B, Ray C, Hayashi T, Bermingham McDonogh O, Reh T. Acheate-scute like 1 (Ascl1) is required for normal delta-like (Dll) gene expression and notch signaling during retinal development. Dev Dyn. 2009;238:2163-78 pubmed publisher
    ..Thus, these results suggest a molecular mechanism whereby attenuated Notch levels coupled with reduced proneurogenic activity in progenitors leads to increased gliogenesis and decreased neurogenesis in the Ascl1-deficient retina. ..
  58. Ishibashi M, Ang S, Shiota K, Nakanishi S, Kageyama R, Guillemot F. Targeted disruption of mammalian hairy and Enhancer of split homolog-1 (HES-1) leads to up-regulation of neural helix-loop-helix factors, premature neurogenesis, and severe neural tube defects. Genes Dev. 1995;9:3136-48 pubmed
    ..These results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis. ..
  59. Baek J, Hatakeyama J, Sakamoto S, Ohtsuka T, Kageyama R. Persistent and high levels of Hes1 expression regulate boundary formation in the developing central nervous system. Development. 2006;133:2467-76 pubmed
    ..We now report that in mice the bHLH factor Hes1 is persistently expressed at high levels by boundary cells but at variable levels by non-boundary cells...
  60. Grbavec D, Stifani S. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Biochem Biophys Res Commun. 1996;223:701-5 pubmed
    ..These results show that Groucho/TLE proteins and Hairy-like/HES proteins are involved in similar interactions in Drosophila and mammals and further suggest that these proteins perform conserved cellular functions. ..
  61. Nakazaki H, Reddy A, Mania Farnell B, Shen Y, Ichi S, McCabe C, et al. Key basic helix-loop-helix transcription factor genes Hes1 and Ngn2 are regulated by Pax3 during mouse embryonic development. Dev Biol. 2008;316:510-23 pubmed publisher
    ..experiments and electro-mobility shift assays, we show that Pax3 regulates Hairy and enhancer of split homolog-1 (Hes1) and Neurogenin2 (Ngn2) by directly binding to their promoters...
  62. Julian E, Dave R, Robson J, Hallahan A, Wainwright B. Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma. Oncogene. 2010;29:3465-76 pubmed publisher
    ..Hedgehog-dependent medulloblastoma were not blocked by loss of RBP-J, indicating that canonical Notch signaling is not required for tumor initiation and growth in this model. ..
  63. Adolphe C, Hetherington R, Ellis T, Wainwright B. Patched1 functions as a gatekeeper by promoting cell cycle progression. Cancer Res. 2006;66:2081-8 pubmed
    ..quot; In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors. ..
  64. de la Pompa J, Wakeham A, Correia K, Samper E, Brown S, Aguilera R, et al. Conservation of the Notch signalling pathway in mammalian neurogenesis. Development. 1997;124:1139-48 pubmed
    ..Our results demonstrate conservation of the Notch pathway and its regulatory mechanisms from fly to mouse, and support a role for the murine Notch signalling pathway in the regulation of neural stem cell differentiation. ..
  65. Takebayashi K, Sasai Y, Sakai Y, Watanabe T, Nakanishi S, Kageyama R. Structure, chromosomal locus, and promoter analysis of the gene encoding the mouse helix-loop-helix factor HES-1. Negative autoregulation through the multiple N box elements. J Biol Chem. 1994;269:5150-6 pubmed
    ..Furthermore, when the N box sequences are disrupted, this negative regulation is severely impaired. These results raise the possibility that HES-1 gene expression may be negatively autoregulated through the N box sequences. ..
  66. Hitoshi S, Alexson T, Tropepe V, Donoviel D, Elia A, Nye J, et al. Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells. Genes Dev. 2002;16:846-58 pubmed
    ..These data are consistent with a role for Notch signaling in the maintenance of the neural stem cell, and inconsistent with a role in a neuronal/glial fate switch. ..
  67. Murphy P, Lu G, Shiah S, Bollen A, Wang R. Endothelial Notch signaling is upregulated in human brain arteriovenous malformations and a mouse model of the disease. Lab Invest. 2009;89:971-82 pubmed publisher
    ..We examined the expression of the canonical Notch downstream target Hes1 in the endothelium of human BAVMs by immunofluorescence, and showed increased levels relative to either autopsy or ..
  68. Ohtsuka T, Sakamoto M, Guillemot F, Kageyama R. Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain. J Biol Chem. 2001;276:30467-74 pubmed
    ..Here, we found that transient misexpression of the basic helix-loop-helix genes Hes1 and Hes5 keeps embryonal telencephalic cells undifferentiated although they have been shown to induce gliogenesis ..
  69. Fujikura J, Hosoda K, Iwakura H, Tomita T, Noguchi M, Masuzaki H, et al. Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreas. Cell Metab. 2006;3:59-65 pubmed
    ..Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas. ..
  70. Cau E, Gradwohl G, Casarosa S, Kageyama R, Guillemot F. Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development. 2000;127:2323-32 pubmed
    We have characterised the functions of the bHLH transcriptional repressors HES1 and HES5 in neurogenesis, using the development of the olfactory placodes in mouse embryos as a model...