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Title

Slit/Robo Signaling Modulates the Proliferation of Central Nervous System Progenitors

AuthorsBorrell, V.; Cárdenas, Adrián; Ciceri, Gabriele; Galcerán, Joan; Flames, Nuria ; Pla, Ramón; Nóbrega-Pereira, S.; García-Frigola, Cristina; Peregrin, Sandra; Zhao, Zhen; Ma, L.; Tessier-Lavigne, M.; Marín Parra, Óscar
Issue Date2012
PublisherCell Press
CitationNeuron 76(2): 338-352 (2012)
AbstractNeurogenesis relies on a delicate balance between progenitor maintenance and neuronal production. Progenitors divide symmetrically to increase the pool of dividing cells. Subsequently, they divide asymmetrically to self-renew and produce new neurons or, in some brain regions, intermediate progenitor cells (IPCs). Here we report that central nervous system progenitors express Robo1 and Robo2, receptors for Slit proteins that regulate axon guidance, and that absence of these receptors or their ligands leads to loss of ventricular mitoses. Conversely, production of IPCs is enhanced in Robo1/2 and Slit1/2 mutants, suggesting that Slit/Robo signaling modulates the transition between primary and intermediate progenitors. Unexpectedly, these defects do not lead to transient overproduction of neurons, probably because supernumerary IPCs fail to detach from the ventricular lining and cycle very slowly. At the molecular level, the role of Slit/Robo in progenitor cells involves transcriptional activation of the Notch effector Hes1. These findings demonstrate that Robo signaling modulates progenitor cell dynamics in the developing brain. Video Abstract: Borrell et al. demonstrate that Slit-Robo signaling regulates the progression from radial glia to intermediate progenitor cells in the embryonic mouse cerebral cortex. Robo effects are mediated by regulation of Hes1 transcription independently of, and synergistically to, Notch. © 2012 Elsevier Inc.
URIhttp://hdl.handle.net/10261/71532
DOI10.1016/j.neuron.2012.08.003
Identifiersdoi: 10.1016/j.neuron.2012.08.003
issn: 0896-6273
e-issn: 1097-4199
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