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Publication : RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration.

First Author  Malagelada C Year  2011
Journal  J Neurosci Volume  31
Issue  9 Pages  3186-96
PubMed ID  21368030 Mgi Jnum  J:170677
Mgi Id  MGI:4947139 Doi  10.1523/JNEUROSCI.4011-10.2011
Citation  Malagelada C, et al. (2011) RTP801/REDD1 regulates the timing of cortical neurogenesis and neuron migration. J Neurosci 31(9):3186-96
abstractText  The generation, differentiation, and migration of newborn neurons are critical features of normal brain development that are subject to both extracellular and intracellular regulation. However, the means of such control are only partially understood. Here, we show that expression of RTP801/REDD1, an inhibitor of mTOR (mammalian target of rapamycin) activation, is regulated during neuronal differentiation and that RTP801 functions to influence the timing of both neurogenesis and neuron migration. RTP801 levels are high in embryonic cortical neuroprogenitors, diminished in newborn neurons, and low in mature neurons. Knockdown of RTP801 in vitro and in vivo accelerates cell cycle exit by neuroprogenitors and their differentiation into neurons. It also disrupts migration of rat newborn neurons to the cortical plate and results in the ectopic localization of mature neurons. On the other hand, RTP801 overexpression delays neuronal differentiation. These findings suggest that endogenous RTP801 plays an essential role in temporal control of cortical development and in cortical patterning.
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