Journal
NEURON
Volume 31, Issue 4, Pages 557-568Publisher
CELL PRESS
DOI: 10.1016/S0896-6273(01)00395-6
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Funding
- NCRR NIH HHS [P41 RR001192] Funding Source: Medline
- PHS HHS [MS30532-05] Funding Source: Medline
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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.
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