Slit/Robo Signaling Modulates the Proliferation of Central Nervous System Progenitors
| Autor: | Gabriele Ciceri, Víctor Borrell, Oscar Marín, Nuria Flames, Ramón Pla, Le Ma, Joan Galcerán, Sandra Peregrín, Zhen Zhao, Sandrina Nóbrega-Pereira, Marc Tessier-Lavigne, Cristina García-Frigola, Adrián Cárdenas |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Central Nervous System
Neuroscience(all) Neurogenesis Green Fluorescent Proteins Cell Count Mice Transgenic Neocortex Nerve Tissue Proteins Biology Transfection Article Mice SLIT1 Basic Helix-Loop-Helix Transcription Factors Animals Progenitor cell HES1 Receptors Immunologic Cells Cultured Progenitor Cell Proliferation Homeodomain Proteins Neurons Chi-Square Distribution General Neuroscience Stem Cells Cell Cycle Gene Expression Regulation Developmental Cadherins Embryo Mammalian Slit Slit-Robo Cell biology Mice Inbred C57BL Mutation Intercellular Signaling Peptides and Proteins Transcription Factor HES-1 Axon guidance Signal Transduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | Neurogenesis 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. Supported by grants from Spanish Ministry of Economy and Innovation MINECO (SAF2011-28845 and CONSOLIDER CSD2007-00023) to O.M. R01 NIH(NINDS) to L.M., and MINECO (SAF2009-07367) and the International Human Frontier Science Program Organization to V.B. A.C. and G.C. are recipients of a >Formacion de Personal Investigador> (FPI) fellowship from the MINECO. |
| Databáze: | OpenAIRE |
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