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

Sophie Laguesse, Catherine Creppe, Danny D. Nedialkova, Pierre Paul Prévot, Laurence Borgs, Sandra Huysseune, Bénédicte Franco, Guérin Duysens, Nathalie Krusy, Gabsang Lee, Nicolas Thelen, Marc Thiry, Pierre Close, Alain Chariot, Brigitte Malgrange, Sebastian A. Leidel, Juliette D. Godin, Laurent Nguyen

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)553-567
Number of pages15
JournalDevelopmental Cell
Volume35
Issue number5
DOIs
StatePublished - 2015

    Fingerprint

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Laguesse, S., Creppe, C., Nedialkova, D. D., Prévot, P. P., Borgs, L., Huysseune, S., Franco, B., Duysens, G., Krusy, N., Lee, G., Thelen, N., Thiry, M., Close, P., Chariot, A., Malgrange, B., Leidel, S. A., Godin, J. D., & Nguyen, L. (2015). A Dynamic Unfolded Protein Response Contributes to the Control of Cortical Neurogenesis. Developmental Cell, 35(5), 553-567. https://doi.org/10.1016/j.devcel.2015.11.005