A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis
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1
University of Liège, GIGA-Neurosciences, Belgium
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.
Keywords:
Cortex,
upr,
er stress,
Neurogenesis,
Microcephaly
Conference:
12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017.
Presentation Type:
Oral Presentation
Topic:
Development
Citation:
Nguyen
L
(2019). A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis.
Front. Neurosci.
Conference Abstract:
12th National Congress of the Belgian Society for Neuroscience.
doi: 10.3389/conf.fnins.2017.94.00117
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Received:
14 Mar 2017;
Published Online:
25 Jan 2019.
*
Correspondence:
Dr. Laurent Nguyen, University of Liège, GIGA-Neurosciences, Liège, 4000, Belgium, lnguyen@ulg.ac.be