Genomes and Genes
Gene Symbol: Hes5
Description: hes family bHLH transcription factor 5
Alias: bHLHb38, transcription factor HES-5, hairy and enhancer of split 5
- Gazit R, Krizhanovsky V, Ben Arie N. Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway. Development. 2004;131:903-13 pubmed..Moreover, of the two transcriptional repressors known to antagonize Math1, Hes5 (but not Hes1) was downregulated in Math1-null rhombic lip tissue and primary cultures, and was shown to bind MATH1,..
- Shi S, Stanley P. Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways. Proc Natl Acad Sci U S A. 2003;100:5234-9 pubmed..Protein O-fucosyltransferase 1 is therefore an essential core member of Notch signaling pathways in mammals. ..
- Hatakeyama J, Sakamoto S, Kageyama R. Hes1 and Hes5 regulate the development of the cranial and spinal nerve systems. Dev Neurosci. 2006;28:92-101 pubmedThe basic helix-loop-helix genes Hes1 and Hes5, known Notch effectors, regulate the maintenance of neural stem cells and the development of the central nervous system (CNS)...
- Ge C, Liu T, Hou X, Stanley P. In vivo consequences of deleting EGF repeats 8-12 including the ligand binding domain of mouse Notch1. BMC Dev Biol. 2008;8:48 pubmed publisher..While Notch1 is expressed in oocytes and blastocysts, Notch1 signaling via canonical ligands is dispensable during oogenesis, blastogenesis, implantation and gastrulation. ..
- 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..This treatment also reduces Hesr1 and Hesr2 expression by as much as 80%. These results support the hypothesis that Hesr1 and Hesr2 are the downstream mediators of the prosensory function of Notch in early cochlear development. ..
- Kele J, Simplicio N, Ferri A, Mira H, Guillemot F, Arenas E, et al. Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons. Development. 2006;133:495-505 pubmed..These results demonstrate that Ngn2 is uniquely required for the development of midbrain dopaminergic neurons. ..
- 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. ..
- Hatakeyama J, Kageyama R. Notch1 expression is spatiotemporally correlated with neurogenesis and negatively regulated by Notch1-independent Hes genes in the developing nervous system. Cereb Cortex. 2006;16 Suppl 1:i132-7 pubmed..We propose that initiation of Notch1 expression is one of the key features for switch from the symmetric to asymmetric cell divisions of neural stem cells and that this process is negatively regulated by Notch1-independent Hes genes. ..
- 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 in the ..
- Ramos C, Rocha S, Gaspar C, Henrique D. Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord. PLoS ONE. 2010;5:e15515 pubmed publisher..However, Jag1 can only activate Notch signalling within the V1 and dI6 domains, whereas Dll1 can signal to neural progenitors both inside and outside its domains of expression. ..
- Taranova O, Magness S, Fagan B, Wu Y, Surzenko N, Hutton S, et al. SOX2 is a dose-dependent regulator of retinal neural progenitor competence. Genes Dev. 2006;20:1187-202 pubmed
- 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. ..
- Matsushima D, Heavner W, Pevny L. Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6. Development. 2011;138:443-54 pubmed publisher..Collectively, these results demonstrate that precise regulation of the ratio of SOX2 to PAX6 is necessary to ensure accurate progenitor cell specification, and place SOX2 as a decisive factor of neural competence in the retina. ..
- Long J, Garel S, Depew M, Tobet S, Rubenstein J. DLX5 regulates development of peripheral and central components of the olfactory system. J Neurosci. 2003;23:568-78 pubmed..In addition, the mutation has a noncell-autonomous effect on the morphogenesis of mitral cells. ..
- Basak O, Taylor V. Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression. Eur J Neurosci. 2007;25:1006-22 pubmed..the highest levels of Notch-reporter activity have self-renewal capability and multipotency, whereas those lacking Hes5 expression do not form neurospheres in vitro...
- Hartman B, Hayashi T, Nelson B, Bermingham McDonogh O, Reh T. Dll3 is expressed in developing hair cells in the mammalian cochlea. Dev Dyn. 2007;236:2875-83 pubmed..Thus Dll3 may play a role in lateral inhibition similar to that of Dll1 and Jag2. ..
- 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. ..
- 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. ..
- Casarosa S, Fode C, Guillemot F. Mash1 regulates neurogenesis in the ventral telencephalon. Development. 1999;126:525-34 pubmed..effectors of Mash1 function revealed that the Notch ligands Dll1 and Dll3, and the target of Notch signaling Hes5, fail to be expressed in Mash1 mutant ventral telencephalon...
- Akazawa C, Sasai Y, Nakanishi S, Kageyama R. Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem. 1992;267:21879-85 pubmed..These results suggest that the negative regulator HES-5 may play an important role in neural development. ..
- Muto A, Iida A, Satoh S, Watanabe S. The group E Sox genes Sox8 and Sox9 are regulated by Notch signaling and are required for Müller glial cell development in mouse retina. Exp Eye Res. 2009;89:549-58 pubmed publisher..While Notch-Hes5 signaling has been shown to be involved in this developmental process, the presence of Müller glial cells in Hes5-..
- 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..This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior. ..
- Nieto M, Schuurmans C, Britz O, Guillemot F. Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors. Neuron. 2001;29:401-13 pubmed..Together, these results demonstrate that proneural genes are involved in lineage restriction of cortical progenitors, promoting the acquisition of the neuronal fate and inhibiting the astrocytic fate. ..
- Barsi J, Rajendra R, Wu J, Artzt K. Mind bomb1 is a ubiquitin ligase essential for mouse embryonic development and Notch signaling. Mech Dev. 2005;122:1106-17 pubmed..Aberrant neurogenesis is a direct consequence of lowered Hes1 and Hes5 expression resulting from the inability to generate Notch1 intracellular domain (NICD1)...
- 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. ..
- 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 and cause a ..
- Li S, Mark S, Radde Gallwitz K, Schlisner R, Chin M, Chen P. Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development. BMC Dev Biol. 2008;8:20 pubmed publisher..with the expression domains of two known Notch target genes, Hairy and enhancer of split homolog genes Hes1 and Hes5. In combination with the loss of Hes1 or Hes5, genetic inactivation of Hey2 leads to increased numbers of mis-..
- Hartmann D, De Strooper B, Serneels L, Craessaerts K, Herreman A, Annaert W, et al. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet. 2002;11:2615-24 pubmed..Thus, the observed variability, together with recent reports on tissue-specific expression patterns of ADAMs 9, 10 and 17, points to the existence of tissue-specific 'teams' of different proteases exerting alpha-secretase activity. ..
- Hahn K, Johnson J, Beres B, Howard S, Wilson Rawls J. Lunatic fringe null female mice are infertile due to defects in meiotic maturation. Development. 2005;132:817-28 pubmed..This represents a new role for the Notch signaling pathway and lunatic fringe in mammalian folliculogenesis. ..
- Machold R, Kittell D, FISHELL G. Antagonism between Notch and bone morphogenetic protein receptor signaling regulates neurogenesis in the cerebellar rhombic lip. Neural Dev. 2007;2:5 pubmed..Our results provide a mechanism by which a balance between neural induction and maintenance of neural progenitors is achieved in the rhombic lip throughout embryonic development. ..
- 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..Thus, the neuroendocrine differentiation depends on basic helix-loop-helix factors, and Notch/Notch-ligand pathways may be involved in determining the cell differentiation fate in fetal airway epithelium. ..
- 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 negative ..
- Evrard Y, Lun Y, Aulehla A, Gan L, Johnson R. lunatic fringe is an essential mediator of somite segmentation and patterning. Nature. 1998;394:377-81 pubmed
- Donoviel D, Hadjantonakis A, Ikeda M, Zheng H, Hyslop P, Bernstein A. Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev. 1999;13:2801-10 pubmed
- Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R. Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci. 2010;30:3489-98 pubmed publisher..However, a requirement for Notch signaling in the telencephalon was not clear, because in Hes1;Hes3;Hes5 triple-mutant mice, neural stem/progenitor cells are depleted in most regions of the developing CNS, but not in the ..
- Hayashi T, Cunningham D, Bermingham McDonogh O. Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti. Dev Dyn. 2007;236:525-33 pubmed..Thus, in addition to controlling the fate decision between pillar cells and Deiters' cells, we find that Fgfr3 also regulates the width of the sensory epithelium...
- 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 constitutively ..
- 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
- Tang L, Alger H, Pereira F. COUP-TFI controls Notch regulation of hair cell and support cell differentiation. Development. 2006;133:3683-93 pubmed..differentiation in COUP-TFI(-/-) mice and confirmed misregulation of Notch signaling components, including Jag1, Hes5 and in a manner consistent with reduced Notch signaling, and correlated with increases in hair cell and support ..
- Parras C, Schuurmans C, Scardigli R, Kim J, Anderson D, Guillemot F. Divergent functions of the proneural genes Mash1 and Ngn2 in the specification of neuronal subtype identity. Genes Dev. 2002;16:324-38 pubmed
- McNay D, Pelling M, Claxton S, Guillemot F, Ang S. Mash1 is required for generic and subtype differentiation of hypothalamic neuroendocrine cells. Mol Endocrinol. 2006;20:1623-32 pubmed..These data demonstrate that Mash1 is both required for the generation of ventral neuroendocrine neurons as well as playing a central role in subtype specification of these neurons. ..
- 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. ..
- Goto M, Hojo M, Ando M, Kita A, Kitagawa M, Ohtsuka T, et al. Hes1 and Hes5 are required for differentiation of pituicytes and formation of the neurohypophysis in pituitary development. Brain Res. 2015;1625:206-17 pubmed publisher..ventral diencephalon fails to evaginate resulting in complete loss of the posterior pituitary lobe in Hes1(-/-); Hes5(+/-) mutant embryos...
- Wittmann W, Schimmang T, Gunhaga L. Progressive effects of N-myc deficiency on proliferation, neurogenesis, and morphogenesis in the olfactory epithelium. Dev Neurobiol. 2014;74:643-56 pubmed publisher..The phenotype was more pronounced at E13.5, with a complete lack of Hes5-positive progenitor cells, decreased proliferation, and neurogenesis...
- Yamaguchi T, Takada S, Yoshikawa Y, Wu N, McMahon A. T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification. Genes Dev. 1999;13:3185-90 pubmed..Our results suggest that Wnt3a, signaling via Brachyury, modulates a balance between mesodermal and neural cell fates during gastrulation. ..
- 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. ..
- Chenn A, Walsh C. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science. 2002;297:365-9 pubmed
- Tashakori M, Zhang Y, Xiong S, You M, Lozano G. p53 Activity Dominates That of p73 upon Mdm4 Loss in Development and Tumorigenesis. Mol Cancer Res. 2016;14:56-65 pubmed publisher..Genetic characterization of the Mdm4 and p73 interaction during development and tumorigenesis suggests new insight into the role of p53 family members, which may influence treatment options for patients. ..
- Fode C, Ma Q, Casarosa S, Ang S, Anderson D, Guillemot F. A role for neural determination genes in specifying the dorsoventral identity of telencephalic neurons. Genes Dev. 2000;14:67-80 pubmed
- Falcone C, Filippis C, Granzotto M, Mallamaci A. Emx2 expression levels in NSCs modulate astrogenesis rates by regulating EgfR and Fgf9. Glia. 2015;63:412-22 pubmed publisher..It points to Emx2 as a new promising tool for controlling reactive astrogliosis and optimizing cell-based designs for brain repair. ..
- Panaliappan T, Wittmann W, Jidigam V, Mercurio S, Bertolini J, Sghari S, et al. Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and Hes5 upregulation. Development. 2018;145: pubmed publisher..using CRISPR-Cas9, we show that Sox2 activity is crucial for the induction of the neural progenitor gene Hes5 and for subsequent differentiation of the neuronal lineage...
- Shimizu T, Nakazawa M, Kani S, Bae Y, Shimizu T, Kageyama R, et al. Zinc finger genes Fezf1 and Fezf2 control neuronal differentiation by repressing Hes5 expression in the forebrain. Development. 2010;137:1875-85 pubmed publisher..Fezf1- and Fezf2-deficient forebrains display upregulation of Hes5 and downregulation of neurogenin 2, which is known to be negatively regulated by Hes5...
- Pelling M, Anthwal N, McNay D, Gradwohl G, Leiter A, Guillemot F, et al. Differential requirements for neurogenin 3 in the development of POMC and NPY neurons in the hypothalamus. Dev Biol. 2011;349:406-16 pubmed publisher..Given the opposing roles of POMC and NPY neurons in regulating food intake, these results indicate that Ngn3 plays a central role in the generation of neuronal populations controlling energy homeostasis in mice. ..
- Krizhanovsky V, Soreq L, Kliminski V, Ben Arie N. Math1 target genes are enriched with evolutionarily conserved clustered E-box binding sites. J Mol Neurosci. 2006;28:211-29 pubmed..and clustering of MATH1-binding E-boxes only in a subset of differentially expressed genes (Nr2f6, Hras1, and Hes5) in both mouse and man...
- Pattyn A, Simplicio N, van Doorninck J, Goridis C, Guillemot F, Brunet J. Ascl1/Mash1 is required for the development of central serotonergic neurons. Nat Neurosci. 2004;7:589-95 pubmed..Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype. ..
- Zordan P, Croci L, Hawkes R, Consalez G. Comparative analysis of proneural gene expression in the embryonic cerebellum. Dev Dyn. 2008;237:1726-35 pubmed publisher..Their expression domains are only partially overlapping, suggesting that they may contribute selectively to ventricular zone regionalization, giving rise to the diversity of cerebellar GABA neurons and, possibly, Purkinje cell subtypes. ..
- Schwarting G, Gridley T, Henion T. Notch1 expression and ligand interactions in progenitor cells of the mouse olfactory epithelium. J Mol Histol. 2007;38:543-53 pubmed..population of Notch1 (+) olfactory basal cells in embryonic mice that coordinately express both the Notch effector Hes5 and the glycosyltransferase Lfng...
- Cox B, Chai R, Lenoir A, Liu Z, Zhang L, Nguyen D, et al. Spontaneous hair cell regeneration in the neonatal mouse cochlea in vivo. Development. 2014;141:816-29 pubmed publisher..Thus, future studies on the neonatal cochlea might shed light on the competence of supporting cells to regenerate hair cells and on the factors that promote the survival of newly regenerated hair cells. ..
- Li H, Wang D, Shen Q, Schonemann M, Gorski J, Jones K, et al. Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis. Neuron. 2003;40:1105-18 pubmed..Further, these double mutant mice provide an unprecedented viable animal model for severe brain malformations due to defects in neural progenitor cells. ..
- Jahan I, Pan N, Kersigo J, Calisto L, Morris K, Kopecky B, et al. Expression of Neurog1 instead of Atoh1 can partially rescue organ of Corti cell survival. PLoS ONE. 2012;7:e30853 pubmed publisher..In contrast to the previously demonstrated fate plasticity of neurons to differentiate as hair cells, hair cell precursors can be maintained for a limited time by Neurog1 but do not transdifferentiate as neurons. ..
- Golson M, Le Lay J, Gao N, Brämswig N, Loomes K, Oakey R, et al. Jagged1 is a competitive inhibitor of Notch signaling in the embryonic pancreas. Mech Dev. 2009;126:687-99 pubmed publisher..Expression of the Notch modifier Manic Fringe (Mfng) is limited to endocrine precursors, providing a possible explanation for the inhibition of Notch signaling by Jag1 during mid-gestation embryonic pancreas development. ..
- Zechner D, Fujita Y, Hülsken J, Muller T, Walther I, Taketo M, et al. beta-Catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol. 2003;258:406-18 pubmed..beta-Catenin signals are thus essential for the maintenance of proliferation of neuronal progenitors, controlling the size of the progenitor pool, and impinging on the decision of neuronal progenitors to proliferate or to differentiate. ..
- Cobos I, Borello U, Rubenstein J. Dlx transcription factors promote migration through repression of axon and dendrite growth. Neuron. 2007;54:873-88 pubmed