title: Activated Notch2 signaling inhibits differentiation of cerebellar granule neuron precursors by maintaining proliferation.
abstract: In the developing cerebellar cortex, granule neuron precursors (GNPs) proliferate and commence differentiation in a superficial zone, the external granule layer (EGL). The molecular basis of the transition from proliferating precursors to immature differentiating neurons remains unknown. Notch signaling is an evolutionarily conserved pathway regulating the differentiation of precursor cells of many lineages. Notch2 is specifically expressed in proliferating GNPs in the EGL. Treatment of GNPs with soluble Notch ligand Jagged1, or overexpression of activated Notch2 or its downstream target HES1, maintains precursor proliferation. The addition of GNP mitogens Jagged1 or Sonic Hedgehog (Shh) upregulates the expression of HES1, suggesting a role for HES1 in maintaining precursor proliferation.
authors.affiliation: Laboratory of Developmental Neurobiology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Solecki
authors.forename: X L
authors.initials: XL
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Tomoda
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.forename: M E
authors.initials: ME
authors.lastname: Hatten
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics; D000072056:Transcription Factor HES-1; D014162:Transfection
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D049452:Green Fluorescent Proteins; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D007202:Indicators and Reagents; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008164:Luminescent Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D051883:Receptor, Notch2; D011956:Receptors, Cell Surface; D000072099:Serrate-Jagged Proteins; D015534:Trans-Activators; D000072056:Transcription Factor HES-1; C489734:Hes1 protein, mouse; C000606274:Jag1 protein, mouse; C497765:Notch2 protein, mouse