期刊
DEVELOPMENT
卷 138, 期 23, 页码 5223-5234出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.063776
关键词
Reelin; Notch; Radial glia; Cortex development; Mouse
资金
- Generalitat Valenciana-Prometeo [2008-134]
- Spanish Ministry of Science and Innovation [SAF2004-07685]
- Fundacion Medica Mutua Madrilena
- Spanish National Research Council (CSIC)
Migration of neurons during cortical development is often assumed to rely on purely post-proliferative reelin signaling. However, Notch signaling, long known to regulate neural precursor formation and maintenance, is required for the effects of reelin on neuronal migration. Here, we show that reelin gain-of-function causes a higher expression of Notch target genes in radial glia and accelerates the production of both neurons and intermediate progenitor cells. Converse alterations correlate with reelin loss-of-function, consistent with reelin controlling Notch signaling during neurogenesis. Ectopic expression of reelin in isolated clones of progenitors causes a severe reduction in neuronal differentiation. In mosaic cell cultures, reelin-primed progenitor cells respond to wild-type cells by further decreasing neuronal differentiation, consistent with an increased sensitivity to lateral inhibition. These results indicate that reelin and Notch signaling cooperate to set the pace of neocortical neurogenesis, a prerequisite for proper neuronal migration and cortical layering.
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