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Publication : A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis.

First Author  Laguesse S Year  2015
Journal  Dev Cell Volume  35
Issue  5 Pages  553-67
PubMed ID  26651292 Mgi Jnum  J:240003
Mgi Id  MGI:5882180 Doi  10.1016/j.devcel.2015.11.005
Citation  Laguesse S, et al. (2015) A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis. Dev Cell 35(5):553-67
abstractText  The cerebral cortex contains layers of neurons sequentially generated by distinct lineage-related progenitors. At the onset of corticogenesis, the first-born progenitors are apical progenitors (APs), whose asymmetric division gives birth directly to neurons. Later, they switch to indirect neurogenesis by generating intermediate progenitors (IPs), which give rise to projection neurons of all cortical layers. While a direct lineage relationship between APs and IPs has been established, the molecular mechanism that controls their transition remains elusive. Here we show that interfering with codon translation speed triggers ER stress and the unfolded protein response (UPR), further impairing the generation of IPs and leading to microcephaly. Moreover, we demonstrate that a progressive downregulation of UPR in cortical progenitors acts as a physiological signal to amplify IPs and promotes indirect neurogenesis. Thus, our findings reveal a contribution of UPR to cell fate acquisition during mammalian brain development.
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