Hes5

Summary

Gene Symbol: Hes5
Description: hairy and enhancer of split 5 (Drosophila)
Alias: bHLHb38, transcription factor HES-5
Species: mouse

Top Publications

  1. ncbi Presenilin-1 regulates neuronal differentiation during neurogenesis
    M Handler
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Development 127:2593-606. 2000
  2. ncbi The role of presenilin 1 during somite segmentation
    K Koizumi
    Department of Molecular Embryology, Graduate School of Medicine, Chiba University, Chuo Ku, Chiba 260 8670, Japan
    Development 128:1391-402. 2001
  3. ncbi APP processing and synaptic plasticity in presenilin-1 conditional knockout mice
    H Yu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Neuron 31:713-26. 2001
  4. ncbi Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system
    C Akazawa
    Institute for Immunology, Kyoto University Faculty of Medicine, Japan
    J Biol Chem 267:21879-85. 1992
  5. ncbi 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
    M Ishibashi
    Institute for Immunology, Kyoto University Faculty of Medicine, Japan
    Genes Dev 9:3136-48. 1995
  6. ncbi Conservation of the Notch signalling pathway in mammalian neurogenesis
    J L de la Pompa
    Amgen Institute, Toronto, Ontario, Canada
    Development 124:1139-48. 1997
  7. ncbi lunatic fringe is an essential mediator of somite segmentation and patterning
    Y A Evrard
    Department of Biochemistry and Molecular Biology and Program in Genes and Development, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Nature 394:377-81. 1998
  8. ncbi Mash1 regulates neurogenesis in the ventral telencephalon
    S Casarosa
    IGBMC, CNRS INSERM Universite Louis Pasteur, BP 163, CU de Strasbourg, France
    Development 126:525-34. 1999
  9. pmc Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation
    T Ohtsuka
    Institute for Virus Research, Kyoto University, Shogoin Kawahara, Sakyo ku, Kyoto 606 8507, USA
    EMBO J 18:2196-207. 1999
  10. pmc Mice lacking both presenilin genes exhibit early embryonic patterning defects
    D B Donoviel
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
    Genes Dev 13:2801-10. 1999

Research Grants

  1. The Role of Sonic Hedgehog in telencephalic patterning
    Robert Machold; Fiscal Year: 2004
  2. Beta-catenin regulation of neural cell fate
    Anjen Chenn; Fiscal Year: 2008
  3. Migration of early olfactory neuronal progenitors
    GERALD SCHWARTING; Fiscal Year: 2009

Scientific Experts

Detail Information

Publications121 found, 100 shown here

  1. ncbi Presenilin-1 regulates neuronal differentiation during neurogenesis
    M Handler
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Development 127:2593-606. 2000
    ..In the ventricular zone of PS1(-/-) mice, expression of the Notch1 downstream effector gene Hes5 is reduced and expression of the Notch1 ligand Dll1 is elevated, whereas expression of Notch1 is unchanged...
  2. ncbi The role of presenilin 1 during somite segmentation
    K Koizumi
    Department of Molecular Embryology, Graduate School of Medicine, Chiba University, Chuo Ku, Chiba 260 8670, Japan
    Development 128:1391-402. 2001
    ..and the expression of several genes involved in the Notch signalling pathway was altered, including Delta-like3, Hes5, lunatic fringe (Lfng) and Mesp2...
  3. ncbi APP processing and synaptic plasticity in presenilin-1 conditional knockout mice
    H Yu
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Neuron 31:713-26. 2001
    ..Expression of Notch downstream effector genes, Hes1, Hes5, and Dll1, is unaffected in the cKO cortex...
  4. ncbi Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system
    C Akazawa
    Institute for Immunology, Kyoto University Faculty of Medicine, Japan
    J Biol Chem 267:21879-85. 1992
    ..These results suggest that the negative regulator HES-5 may play an important role in neural development...
  5. ncbi 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
    M Ishibashi
    Institute for Immunology, Kyoto University Faculty of Medicine, Japan
    Genes Dev 9:3136-48. 1995
    ..These results suggest that HES-1 normally controls the proper timing of neurogenesis and regulates neural tube morphogenesis...
  6. ncbi Conservation of the Notch signalling pathway in mammalian neurogenesis
    J L de la Pompa
    Amgen Institute, Toronto, Ontario, Canada
    Development 124:1139-48. 1997
    ..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...
  7. ncbi lunatic fringe is an essential mediator of somite segmentation and patterning
    Y A Evrard
    Department of Biochemistry and Molecular Biology and Program in Genes and Development, University of Texas, M D Anderson Cancer Center, Houston 77030, USA
    Nature 394:377-81. 1998
    ....
  8. ncbi Mash1 regulates neurogenesis in the ventral telencephalon
    S Casarosa
    IGBMC, CNRS INSERM Universite Louis Pasteur, BP 163, CU de Strasbourg, France
    Development 126:525-34. 1999
    ..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...
  9. pmc Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation
    T Ohtsuka
    Institute for Virus Research, Kyoto University, Shogoin Kawahara, Sakyo ku, Kyoto 606 8507, USA
    EMBO J 18:2196-207. 1999
    ..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 ..
  10. pmc Mice lacking both presenilin genes exhibit early embryonic patterning defects
    D B Donoviel
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
    Genes Dev 13:2801-10. 1999
    ....
  11. ncbi Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium
    E Cau
    IGBMC, CNRS INSERM Universite Louis Pasteur, BP 163, CU de Strasbourg, France
    Development 127:2323-32. 2000
    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...
  12. ncbi Glial cell fate specification modulated by the bHLH gene Hes5 in mouse retina
    M Hojo
    Institute for Virus Research, Kyoto University and Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo ku, Kyoto 606 8507, Japan
    Development 127:2515-22. 2000
    ..Here, we found that, in mouse retina, the bHLH gene Hes5 was specifically expressed by differentiating Müller glial cells and that misexpression of Hes5 with recombinant ..
  13. ncbi Basic helix-loop-helix transcription factors regulate the neuroendocrine differentiation of fetal mouse pulmonary epithelium
    T Ito
    Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan
    Development 127:3913-21. 2000
    ..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...
  14. ncbi Neural bHLH genes control the neuronal versus glial fate decision in cortical progenitors
    M Nieto
    Institut de Génétique et de Biologie Moléculaire, et Cellulaire, CNRS, INSERM, Universite, Louis Pasteur, Boite Postale 163, 67404 Illkirch Cedex, Communauté urbaine de, Strasbourg, France
    Neuron 29:401-13. 2001
    ..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...
  15. ncbi Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain
    T Ohtsuka
    Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    J Biol Chem 276:30467-74. 2001
    ..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 ..
  16. ncbi Hes1 and Hes5 activities are required for the normal development of the hair cells in the mammalian inner ear
    A Zine
    Institute of Physiology, University of Lausanne, 1005 Lausanne, Switzerland
    J Neurosci 21:4712-20. 2001
    ..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 ..
  17. ncbi Notch1 is required for neuronal and glial differentiation in the cerebellum
    Simone Lütolf
    Institute of Cell Biology, Department of Biology, Swiss Federal Institute of Technology, CH 8093 Zurich, Switzerland
    Development 129:373-85. 2002
    ..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...
  18. pmc Notch pathway molecules are essential for the maintenance, but not the generation, of mammalian neural stem cells
    Seiji Hitoshi
    Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Genes Dev 16:846-58. 2002
    ..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...
  19. ncbi The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts
    Dieter Hartmann
    Center for Human Genetics KU Leuven and Flanders Interuniversity Institute for Biotechnology, VIB 4 KU Leuven, VIB 7 Celgen, Herestraat 49, 3000 Leuven, Belgium
    Hum Mol Genet 11:2615-24. 2002
    ..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...
  20. ncbi DLX5 regulates development of peripheral and central components of the olfactory system
    Jason E Long
    Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, Langley Porter Psychiatric Institute, University of California, San Francisco, San Francisco, California 94143 0984, USA
    J Neurosci 23:568-78. 2003
    ..In addition, the mutation has a noncell-autonomous effect on the morphogenesis of mitral cells...
  21. pmc Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways
    Shaolin Shi
    Department of Cell Biology, Albert Einstein College Medicine, New York, NY 10461, USA
    Proc Natl Acad Sci U S A 100:5234-9. 2003
    ..Protein O-fucosyltransferase 1 is therefore an essential core member of Notch signaling pathways in mammals...
  22. ncbi Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development
    Ryosuke Tsunematsu
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    J Biol Chem 279:9417-23. 2004
    ..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...
  23. ncbi Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation
    Jun Hatakeyama
    Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Development 131:5539-50. 2004
    ..Here, we report that inactivation of Hes1 and Hes5, known Notch effectors, and additional inactivation of Hes3 extensively accelerate cell differentiation and cause a ..
  24. ncbi Mind bomb1 is a ubiquitin ligase essential for mouse embryonic development and Notch signaling
    Julius C Barsi
    Institute for Cellular and Molecular Biology MBB 2 124, Section of Molecular Genetics and Microbiology, The University of Texas at Austin, Austin, TX 78712, USA
    Mech Dev 122:1106-17. 2005
    ..Aberrant neurogenesis is a direct consequence of lowered Hes1 and Hes5 expression resulting from the inability to generate Notch1 intracellular domain (NICD1)...
  25. ncbi Notch signaling coordinates the patterning of striatal compartments
    Heather A Mason
    Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016, USA
    Development 132:4247-58. 2005
    ..These results indicate that Notch signaling is required in neural progenitor cells to control cell fate in the striatum, but is dispensable during subsequent phases of neuronal migration and differentiation...
  26. ncbi Retinal ganglion cell-derived sonic hedgehog locally controls proliferation and the timing of RGC development in the embryonic mouse retina
    Yaping Wang
    Molecular Medicine Program, Ottawa Health Research Institute and University of Ottawa Eye Institute, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada
    Development 132:5103-13. 2005
    ....
  27. ncbi Hes1 and Hes5 regulate the development of the cranial and spinal nerve systems
    Jun Hatakeyama
    Institute for Virus Research, Kyoto University, Kyoto, Japan
    Dev Neurosci 28:92-101. 2006
    The 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)...
  28. pmc SOX2 is a dose-dependent regulator of retinal neural progenitor competence
    Olena V Taranova
    Department of Genetics, University of North Carolina at Chapel Hill, NC 27599, USA
    Genes Dev 20:1187-202. 2006
    ....
  29. ncbi Notch1 expression is spatiotemporally correlated with neurogenesis and negatively regulated by Notch1-independent Hes genes in the developing nervous system
    Jun Hatakeyama
    Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Cereb Cortex 16:i132-7. 2006
    ..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...
  30. ncbi Loss of Fgfr3 leads to excess hair cell development in the mouse organ of Corti
    Toshinori Hayashi
    Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology HNS, University of Washington, Seattle, Washington 98195, USA
    Dev Dyn 236:525-33. 2007
    ..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...
  31. ncbi Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression
    Onur Basak
    Department of Molecular Embryology, Max Planck Institute of Immunobiology, Stubeweg 51, 79108 Freiburg, Germany
    Eur J Neurosci 25:1006-22. 2007
    ..the highest levels of Notch-reporter activity have self-renewal capability and multipotency, whereas those lacking Hes5 expression do not form neurospheres in vitro...
  32. pmc Dlx-dependent and -independent regulation of olfactory bulb interneuron differentiation
    Jason E Long
    Nina Ireland Laboratory of Developmental Neurobiology, University of California at San Francisco, San Francisco, California 94143, USA
    J Neurosci 27:3230-43. 2007
    ....
  33. ncbi Dll3 is expressed in developing hair cells in the mammalian cochlea
    Byron H Hartman
    Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA
    Dev Dyn 236:2875-83. 2007
    ..Thus Dll3 may play a role in lateral inhibition similar to that of Dll1 and Jag2...
  34. pmc Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea
    Toshinori Hayashi
    Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology HNS, Box 357923, USA
    Dev Biol 316:87-99. 2008
    ..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...
  35. pmc Hey2 functions in parallel with Hes1 and Hes5 for mammalian auditory sensory organ development
    Shuangding Li
    Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
    BMC Dev Biol 8:20. 2008
    ..This study explores the expression and function of a putative Notch target gene...
  36. pmc In vivo consequences of deleting EGF repeats 8-12 including the ligand binding domain of mouse Notch1
    Changhui Ge
    Department of Cell Biology, Albert Einstein College of Medicine, New York, NY 10461, USA
    BMC Dev Biol 8:48. 2008
    ..We also show that maternal and zygotic Notch1(lbd/lbd) mutant embryos develop through gastrulation to mid-gestation...
  37. pmc Acheate-scute like 1 (Ascl1) is required for normal delta-like (Dll) gene expression and notch signaling during retinal development
    Branden R Nelson
    Department of Biological Structure, School of Medicine, University of Washington, Seattle, Washington 98195, USA
    Dev Dyn 238:2163-78. 2009
    ..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...
  38. doi The group E Sox genes Sox8 and Sox9 are regulated by Notch signaling and are required for Müller glial cell development in mouse retina
    Akihiko Muto
    Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokane dai, Minato ku, Tokyo 108 8639, Japan
    Exp Eye Res 89:549-58. 2009
    ..While Notch-Hes5 signaling has been shown to be involved in this developmental process, the presence of Müller glial cells in Hes5-..
  39. doi Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains
    Itaru Imayoshi
    Institute for Virus Research, Kyoto University, Sakyo ku, Kyoto, Japan
    J Neurosci 30:3489-98. 2010
    ..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 ..
  40. doi Canonical Notch signaling is not required for the growth of Hedgehog pathway-induced medulloblastoma
    E Julian
    Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia
    Oncogene 29:3465-76. 2010
    ..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...
  41. pmc Notch signaling specifies prosensory domains via lateral induction in the developing mammalian inner ear
    Byron H Hartman
    Department of Biological Structure, University of Washington, Seattle, 98195, USA
    Proc Natl Acad Sci U S A 107:15792-7. 2010
    ..These results support a model where activation of Notch and propagation through lateral induction promote prosensory character in specific regions of the developing otocyst...
  42. pmc Two Notch ligands, Dll1 and Jag1, are differently restricted in their range of action to control neurogenesis in the mammalian spinal cord
    Catarina Ramos
    Faculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Lisboa, Portugal
    PLoS ONE 5:e15515. 2010
    ..However, the specific contribution of different ligands to regulate neurogenesis in vertebrate embryos is still poorly understood...
  43. pmc Combinatorial regulation of optic cup progenitor cell fate by SOX2 and PAX6
    Danielle Matsushima
    UNC Neuroscience Center, University of North Carolina at Chapel Hill, NC 27599, USA
    Development 138:443-54. 2011
    ..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...
  44. pmc Fbxw7-dependent degradation of Notch is required for control of "stemness" and neuronal-glial differentiation in neural stem cells
    Akinobu Matsumoto
    Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka, Fukuoka 812 8582, Japan
    J Biol Chem 286:13754-64. 2011
    ..Our results thus implicate Fbxw7 as a key regulator of the maintenance and differentiation of neural stem cells in the brain...
  45. doi Rbpj regulates development of prosensory cells in the mammalian inner ear
    Norio Yamamoto
    Laboratory of Cochlear Development, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, NIDCD, NIH, Bethesda, MD 20892, USA
    Dev Biol 353:367-79. 2011
    ..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...
  46. ncbi Math1 controls cerebellar granule cell differentiation by regulating multiple components of the Notch signaling pathway
    Roi Gazit
    Cell and Animal Biology, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
    Development 131:903-13. 2004
    ..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,..
  47. ncbi Lunatic fringe null female mice are infertile due to defects in meiotic maturation
    Katherine L Hahn
    Molecular and Cellular Graduate Program, Arizona State University, Tempe, AZ 85284 4501, USA
    Development 132:817-28. 2005
    ..This represents a new role for the Notch signaling pathway and lunatic fringe in mammalian folliculogenesis...
  48. ncbi COUP-TFI controls Notch regulation of hair cell and support cell differentiation
    Louisa S Tang
    Huffington Center on Aging, Department of Otolaryngology Head and Neck Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Development 133:3683-93. 2006
    ..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 ..
  49. pmc Progenitor cell proliferation in the retina is dependent on Notch-independent Sonic hedgehog/Hes1 activity
    Dana S Wall
    Ottawa Health Research Institute, Ottawa, Ontario, Canada
    J Cell Biol 184:101-12. 2009
    ..This paper is the first demonstration of the mechanistic and functional link between Shh, Gli, and Hes1 in the regulation of progenitor cell behavior...
  50. ncbi Neurogenin 2 is required for the development of ventral midbrain dopaminergic neurons
    Julianna Kele
    Laboratory of Molecular Neurobiology, MBB, Karolinska Institutet, Retzius building A1, Stockholm, Sweden
    Development 133:495-505. 2006
    ..These results demonstrate that Ngn2 is uniquely required for the development of midbrain dopaminergic neurons...
  51. ncbi Multiple roles of mouse Numb in tuning developmental cell fates
    O Zilian
    Swiss Institute for Experimental Cancer Research ISREC, 155 Chemin des Boveresses, CH 1066 Epalinges s Lausanne, Switzerland
    Curr Biol 11:494-501. 2001
    ..Although overexpression experiments suggested that Numb might also antagonize some Notch activity in vertebrates, the developmental processes in which Numb is involved remained elusive...
  52. pmc Cdx2 is essential for axial elongation in mouse development
    Kallayanee Chawengsaksophak
    Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada M5G 1X5
    Proc Natl Acad Sci U S A 101:7641-5. 2004
    ..The gene appears to be important in the integration of the pathways controlling embryonic axial elongation, and anterior-posterior patterning...
  53. pmc Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates
    Esther Maier
    Umeå Center for Molecular Medicine, Building 6M, 4th Floor, Umea University, Umea, Sweden
    Development 137:1601-11. 2010
    ..In summary, we present a conserved mechanism in amniotes in which Bmp and Fgf signals act in an opposing manner to regulate the respiratory versus sensory epithelial cell fate decision...
  54. pmc Notch signaling is not essential in sonic hedgehog-activated medulloblastoma
    B A Hatton
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
    Oncogene 29:3865-72. 2010
    ..of medulloblastomas driven by the SmoA1 transgene was unchanged by the bi-allelic absence of Notch1, Notch2, or Hes5 genes...
  55. doi The small GTPase RhoA is required to maintain spinal cord neuroepithelium organization and the neural stem cell pool
    Dominik Herzog
    Institute of Cell Biology, Department of Biology, Eidgenossische Technische Hochschule Zurich, CH 8093 Zurich, Switzerland
    J Neurosci 31:5120-30. 2011
    ..Together, our data show that RhoA signaling is necessary for AJ regulation and for the maintenance of mammalian neuroepithelium organization preventing precocious cell-cycle exit and differentiation...
  56. pmc NFIX Regulates Proliferation and Migration Within the Murine SVZ Neurogenic Niche
    Yee Hsieh Evelyn Heng
    The School of Biomedical Sciences
    Cereb Cortex 25:3758-78. 2015
    ..Collectively, these findings suggest that NFIX regulates both proliferation and migration during the development of the SVZ neurogenic niche. ..
  57. pmc Presenilin-1 knockin mice reveal loss-of-function mechanism for familial Alzheimer's disease
    Dan Xia
    Center for Neurologic Diseases, Department of Neurology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA Center for Human Genetic Research, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Neuron 85:967-81. 2015
    ..Collectively, our findings reveal that FAD mutations can cause complete loss of Presenilin-1 function in vivo, suggesting that clinical PSEN mutations produce FAD through a loss-of-function mechanism. ..
  58. doi Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo
    Toshinao Oyama
    Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, 1 8 1 Inohana, Chuo Ku, Chiba 260 8670, Japan
    Development 138:5235-46. 2011
    ..These results indicate that engagement of Mam is essential for Notch signaling, and that the three Mam isoforms have distinct roles in vivo...
  59. doi The role of Hes genes in intestinal development, homeostasis and tumor formation
    Taro Ueo
    Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto 606 8501, Japan
    Development 139:1071-82. 2012
    ..Here we found that inactivation of the Notch effectors Hes1, Hes3 and Hes5, but not Hes1 alone, led to reduced cell proliferation, increased secretory cell formation and altered intestinal ..
  60. ncbi Gde2 regulates cortical neuronal identity by controlling the timing of cortical progenitor differentiation
    Marianeli Rodriguez
    The Solomon Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, PCTB1004, 725 N Wolfe Street, Baltimore, MD 21205, USA
    Development 139:3870-9. 2012
    ....
  61. doi BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets
    Luca Tiberi
    Universite Libre de Bruxelles, Institute for Interdisciplinary Research, ULB Neuroscience Institute, Brussels, Belgium
    Nat Neurosci 15:1627-35. 2012
    ..promoted the neurogenic conversion by switching the composition of Notch-dependent transcriptional complexes at the Hes5 promoter...
  62. pmc Numb is required for the production of terminal asymmetric cell divisions in the developing mouse retina
    Amel Kechad
    Cellular Neurobiology Research Unit, Institut de Recherches Cliniques de Montreal, Montreal, Quebec H2W 1R7, Canada
    J Neurosci 32:17197-210. 2012
    ....
  63. pmc Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling
    Jordi Guiu
    Program in Cancer Research, Hospital del Mar Medical Research Institute, IMIM, Barcelona Biomedical Research Park, 08003 Barcelona, Spain
    J Exp Med 210:71-84. 2013
    ..mouse embryo, a function previously undetected as the result of functional compensation by de novo expression of Hes5 in the aorta/gonad/mesonephros (AGM) region of Hes1 mutants...
  64. pmc Role of p63 and the Notch pathway in cochlea development and sensorineural deafness
    Alessandro Terrinoni
    Biochemistry Laboratory Istituto Dermopatico Dell Immacolata, c o Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, 00133 Rome, Italy
    Proc Natl Acad Sci U S A 110:7300-5. 2013
    ..TAp63 transactivates hairy and enhancer of split 5 (Hes5) and atonal homolog 1 (Atoh1), components of the Notch pathway, known to be involved in cochlear neuroepithelial ..
  65. pmc Notch2 regulates BMP signaling and epithelial morphogenesis in the ciliary body of the mouse eye
    Yi Zhou
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    Proc Natl Acad Sci U S A 110:8966-71. 2013
    ..Based on our findings, we propose that Jag1-Notch2 signaling controls CB morphogenesis at least in part by regulating cell proliferation and BMP signaling...
  66. doi Hes1 and Hes5 regulate vascular remodeling and arterial specification of endothelial cells in brain vascular development
    Masashi Kitagawa
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Sakyo ku, Kyoto 606 8507, Japan
    Mech Dev 130:458-66. 2013
    ..The bHLH genes Hes1 and Hes5 are essential effectors for Notch signaling, which regulate the maintenance of progenitor cells and the timing of ..
  67. ncbi Mesp2 initiates somite segmentation through the Notch signalling pathway
    Y Takahashi
    Cellular and Molecular Toxicology Division, National Institute of Health Sciences, Setagaya Ku, Tokyo, Japan
    Nat Genet 25:390-6. 2000
    ..Therefore, Mesp2- and Ps1-dependent activation of Notch-signalling pathways might differentially regulate Dll1 expression, resulting in the establishment of the rostro-caudal polarity of somites...
  68. pmc The transcription factor Sox10 is a key regulator of peripheral glial development
    S Britsch
    Max Delbruck Center for Molecular Medicine, D 13122 Berlin, Germany
    Genes Dev 15:66-78. 2001
    ..Haploinsufficiency of Sox10 can thus cause pigmentation and megacolon defects, which are also observed in Sox10(Dom)/+ mice and in patients with Waardenburg-Hirschsprung disease caused by heterozygous SOX10 mutations...
  69. ncbi Regulation of cerebral cortical size by control of cell cycle exit in neural precursors
    Anjen Chenn
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Science 297:365-9. 2002
    ....
  70. ncbi Inactivation of Numb and Numblike in embryonic dorsal forebrain impairs neurogenesis and disrupts cortical morphogenesis
    Hua Shun Li
    Howard Hughes Medical Institute, Departments of Physiology and Biochemistry, University of California, San Francisco, San Francisco, CA 94143, USA
    Neuron 40:1105-18. 2003
    ..Further, these double mutant mice provide an unprecedented viable animal model for severe brain malformations due to defects in neural progenitor cells...
  71. ncbi Conversion of biliary system to pancreatic tissue in Hes1-deficient mice
    Ryo Sumazaki
    Department of Child Health, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan
    Nat Genet 36:83-7. 2004
    ..Thus, biliary epithelium has the potential for pancreatic differentiation and Hes1 determines biliary organogenesis by preventing the pancreatic differentiation program, probably by directly repressing transcription of Neurog3...
  72. ncbi Specification of vertebral identity is coupled to Notch signalling and the segmentation clock
    Ralf Cordes
    Institut für Molekularbiologie OE5250, Medizinische Hochschule, Carl Neuberg Str 1, D 30625 Hannover, Germany
    Development 131:1221-33. 2004
    ..Transgenic mice with reduced Notch activity in the presomitic mesoderm as indicated by loss of Hes5 expression were viable and displayed defects in somites and vertebrae consistent with known roles of Notch ..
  73. pmc Loss of cell polarity causes severe brain dysplasia in Lgl1 knockout mice
    Olga Klezovitch
    Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA
    Genes Dev 18:559-71. 2004
    ....
  74. ncbi Ascl1/Mash1 is required for the development of central serotonergic neurons
    Alexandre Pattyn
    CNRS UMR 8542, Ecole Normale Superieure, 75005 Paris, France
    Nat Neurosci 7:589-95. 2004
    ..Thus Ascl1, which is essential for noradrenergic differentiation, is also a determinant of the serotonergic phenotype...
  75. ncbi Math1 target genes are enriched with evolutionarily conserved clustered E-box binding sites
    Valery Krizhanovsky
    Department of Cell and Animal Biology, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    J Mol Neurosci 28:211-29. 2006
    ..and clustering of MATH1-binding E-boxes only in a subset of differentially expressed genes (Nr2f6, Hras1, and Hes5) in both mouse and man...
  76. ncbi dILA neurons in the dorsal spinal cord are the product of terminal and non-terminal asymmetric progenitor cell divisions, and require Mash1 for their development
    Hendrik Wildner
    Max Delbrück Centrum for Molecular Medicine, Berlin Buch, Germany
    Development 133:2105-13. 2006
    ..Our data allow us to assign to Mash1 a function in asymmetric cell divisions, and indicate that the factor coordinates cell cycle exit and specification in the one daughter that gives rise to a dILA neuron...
  77. ncbi Notch and HES5 are regulated during human cartilage differentiation
    Camilla Karlsson
    Institute for Laboratory Medicine, Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
    Cell Tissue Res 327:539-51. 2007
    ..We have characterized the human bHLH gene HES5 and investigated its role during chondrogenesis...
  78. ncbi Appropriate suppression of Notch signaling by Mesp factors is essential for stripe pattern formation leading to segment boundary formation
    Yu Takahashi
    Cellular and Molecular Toxicology Division, National Institute of Health Sciences, 1 18 1 Kamiyoga, Setagayaku, Tokyo 158 8501, Japan
    Dev Biol 304:593-603. 2007
    ..The activation and subsequent suppression of Notch signaling might thus be a crucial event for both stripe pattern formation and boundary formation...
  79. ncbi Six1 is essential for early neurogenesis in the development of olfactory epithelium
    Keiko Ikeda
    Division of Biology, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329 0498, Japan
    Dev Biol 311:53-68. 2007
    ..Expression levels of neurogenin1 (Ngn1) and NeuroD are reduced and those of Hes1 and Hes5 are augmented in the OE of Six1-/- at E10.5...
  80. doi HES1 regulates 5-HT1A receptor gene transcription at a functional polymorphism: essential role in developmental expression
    Kirsten X Jacobsen
    Ottawa Health Research Institute Neuroscience and Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON Canada
    Mol Cell Neurosci 38:349-58. 2008
    Mammalian HES1 and HES5 are abundant in developing CNS and inhibit neurogenesis, while HES6 promotes neurogenesis...
  81. doi Combinatorial signalling controls Neurogenin2 expression at the onset of spinal neurogenesis
    Vanessa Ribes
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, INSERM U 596, CNRS UMR 7104, Universite Louis Pasteur, 1 rue Laurent Fries, Illkirch, BP 10142 F 67400, France
    Dev Biol 321:470-81. 2008
    ..Our data thus support a model where signal integration at the level of a single enhancer constitutes a key mechanism to control the onset of neurogenesis...
  82. pmc Notch signaling maintains Leydig progenitor cells in the mouse testis
    Hao Tang
    The Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA
    Development 135:3745-53. 2008
    ....
  83. doi Fibroblast growth factor-2 increases the expression of neurogenic genes and promotes the migration and differentiation of neurons derived from transplanted neural stem/progenitor cells
    E Vergaño-Vera
    Instituto Cajal, Consejo Superior de Investigaciones Cientificas, Avda Dr Arce 37, E 28002 Madrid, Spain
    Neuroscience 162:39-54. 2009
    ..Hence, the migration and maturation of neurons derived from transplanted NSC can be promoted by upregulating neurogenic gene expression with FGF-2...
  84. pmc Jagged1 is a competitive inhibitor of Notch signaling in the embryonic pancreas
    Maria L Golson
    Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mech Dev 126:687-99. 2009
    ..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...
  85. doi Zinc finger protein 191 (ZNF191/Zfp191) is necessary to maintain neural cells as cycling progenitors
    Olfa Khalfallah
    CRICM UPMC Inserm UMR_S 975 CNRS UMR 7225, Biotechnology and Biotherapy Laboratory F 75005, Paris, France
    Stem Cells 27:1643-53. 2009
    ....
  86. doi Ptch1-mediated dosage-dependent action of Shh signaling regulates neural progenitor development at late gestational stages
    Yayoi Shikata
    Brain Science Institute, RIKEN, 2 1 Hirosawa, Wako, Saitama 351 0198, Japan
    Dev Biol 349:147-59. 2011
    ..These data indicated that endogenous Ptch1 mediates the broad effects of Shh on the transition from VZ progenitors to IPCs and activation of proliferation of the IPCs in the cortex during late gestational stages...
  87. pmc HeyL promotes neuronal differentiation of neural progenitor cells
    Ali Jalali
    Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
    J Neurosci Res 89:299-309. 2011
    ..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...
  88. doi Cooperative functions of Hes/Hey genes in auditory hair cell and supporting cell development
    Tomoko Tateya
    Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    Dev Biol 352:329-40. 2011
    ..While the Notch effector genes Hes1, Hes5 and Hey1 are expressed in the developing cochlea, inactivation of either of them causes only mild abnormality, ..
  89. doi SFRPs act as negative modulators of ADAM10 to regulate retinal neurogenesis
    Pilar Esteve
    Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas Universidad Autonoma de Madrid, Madrid, Spain
    Nat Neurosci 14:562-9. 2011
    ..Together, these data indicate that Sfrps inhibit the ADAM10 metalloprotease, which might have important implications in pathological events, including cancer and Alzheimer's disease...
  90. ncbi Structure and chromosomal locus of the mouse gene encoding a cerebellar Purkinje cell-specific helix-loop-helix factor Hes-3
    T Sakagami
    Institute for Immunology, Kyoto University Faculty of Medicine, Japan
    Biochem Biophys Res Commun 203:594-601. 1994
    ..These results suggest that the Hes-3 and Hes-5 genes may be clustered on chromosome 4 while the Hes-1 gene is not...
  91. ncbi Interaction between Notch signalling and Lunatic fringe during somite boundary formation in the mouse
    I B Barrantes
    Amgen Institute, Ontario Cancer Institute, Departments of Medical Biophysics and Immunology University of Toronto 620 University Avenue, Toronto, Ontario, M5G 2C1, Canada
    Curr Biol 9:470-80. 1999
    ....
  92. ncbi The Phox2b transcription factor coordinately regulates neuronal cell cycle exit and identity
    V Dubreuil
    Laboratoire de Genetique et Physiologie du Developpement, IBDM, CNRS INSERM Universite de la Mediterranee AP de Marseille, Campus de Luminy Case 907, France
    Development 127:5191-201. 2000
    ..These results suggest that Phox2b coordinates quantitative and qualitative aspects of neurogenesis, thus ensuring that neurons of the correct phenotype are generated in proper numbers at the appropriate times and locations...
  93. pmc The murine winged helix transcription factors, Foxc1 and Foxc2, are both required for cardiovascular development and somitogenesis
    T Kume
    Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA
    Genes Dev 15:2470-82. 2001
    ..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...
  94. ncbi Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm
    Sally L Dunwoodie
    Division of Mammalian Development, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Development 129:1795-806. 2002
    ..As the expression of Lfng, Hes1, Hes5 and Hey1 is disrupted in the presomitic mesoderm, we suggest that the somitic aberrations are founded in the ..
  95. ncbi Divergent vascular mechanisms downstream of Sry establish the arterial system in the XY gonad
    Jennifer Brennan
    Duke University Medical Center, Durham, North Carolina 27710, USA
    Dev Biol 244:418-28. 2002
    ..This newly formed arterial system establishes a new pattern of blood flow in the XY gonad, which we speculate may have an important role in export of testosterone to masculinize the XY embryo...
  96. ncbi Overexpression of the Notch target genes Hes in vivo induces lymphoid and myeloid alterations
    Shin Kawamata
    SyStemix Inc 3155 Porter Dr, Palo Alto, CA 94304, USA
    Oncogene 21:3855-63. 2002
    ..Hes-transplanted mice remained healthy but cells transduced with Hes1 or Hes5 were partially impaired in their ability to differentiate into B cells...
  97. ncbi Notch/Notch ligands and Math1 expression patterns in the organ of Corti of wild-type and Hes1 and Hes5 mutant mice
    Azel Zine
    Institute of Physiology, University of Lausanne, 7 rue du Bugnon, CH 1005, Lausanne, Switzerland
    Hear Res 170:22-31. 2002
    ..We demonstrated that Hes1 and Hes5, two members of the inhibitory bHLH transcription factors, act as negative regulators of hair cell differentiation...
  98. ncbi The basic helix-loop-helix genes Hesr1/Hey1 and Hesr2/Hey2 regulate maintenance of neural precursor cells in the brain
    Masami Sakamoto
    Institute for Virus Research, Kyoto University, Kyoto 606 8507, Japan
    J Biol Chem 278:44808-15. 2003
    ..These results indicate that Hesr1 and Hesr2 negatively regulate neuronal bHLH genes, promote maintenance of neural precursor cells, and increase late-born cell types in the developing brain...
  99. ncbi Hes binding to STAT3 mediates crosstalk between Notch and JAK-STAT signalling
    Sachiko Kamakura
    Institute of Molecular and Cellular Biosciences, University of Tokyo, 1 1 1 Yayoi, Bunkyo ku, Tokyo 113 0032, Japan
    Nat Cell Biol 6:547-54. 2004
    ..Here we show that STAT3 is activated in the presence of active Notch, as well as the Notch effectors Hes1 and Hes5. Hes proteins associate with JAK2 and STAT3, and facilitate complex formation between JAK2 and STAT3, thus ..
  100. ncbi Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis
    Petur H Petersen
    Department of Molecular, Cellular and Developmental Biology, Yale University, P O Box 208103, New Haven, Connecticut 06520, USA
    Nat Neurosci 7:803-11. 2004
    ....
  101. ncbi Expression of Hairy/Enhancer of Split genes, Hes1 and Hes5, during murine nephron morphogenesis
    Tino D Piscione
    Program in Developmental Biology, Research Institute, The Hospital for Sick Children, 555 University Ave, Toronto, Ont, Canada M5G 1X8
    Gene Expr Patterns 4:707-11. 2004
    ..define the spatial activation of the Notch pathway in developing nephrons, we analyzed the expression of Hes1 and Hes5 by mRNA in situ hybridization in cryosections of developing kidneys, and compared their spatiotemporal expression ..

Research Grants4

  1. The Role of Sonic Hedgehog in telencephalic patterning
    Robert Machold; Fiscal Year: 2004
    ..This work will hopefully lead to a deeper understanding of regional specification in the developing forebrain. ..
  2. Beta-catenin regulation of neural cell fate
    Anjen Chenn; Fiscal Year: 2008
    ..Cell proliferation, cell cycle exit, cell death and synaptic architecture will be examined by immunohistochemical techniques, and light and electron microscopy. ..
  3. Migration of early olfactory neuronal progenitors
    GERALD SCHWARTING; Fiscal Year: 2009
    ..These studies will lead to an understanding of the complex factors that guide GnRH neurons to their proper destinations in the hypothalamus to control the hypothalamic-pituitary-gonadal axis. ..