Feedback regulation of apical progenitor fate by immature neurons through Wnt7–Celsr3–Fzd3 signalling

Wei Wang, Yves Jossin, Guoliang Chai, Wen-Hui Lien, Fadel Tissir () and Andre M. Goffinet ()
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Wei Wang: Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium
Yves Jossin: Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium
Guoliang Chai: Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium
Wen-Hui Lien: Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 74, Box B1.74.09
Fadel Tissir: Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium
Andre M. Goffinet: Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Sequential generation of neurons and glial cells during development is critical for the wiring and function of the cerebral cortex. This process requires accurate coordination of neural progenitor cell (NPC) fate decisions, by NPC-autonomous mechanisms as well as by negative feedback from neurons. Here, we show that neurogenesis is protracted and gliogenesis decreased in mice with mutations of genes Celsr3 and Fzd3. This phenotype is not due to gene inactivation in progenitors, but rather in immature cortical neurons. Mutant neurons are unable to upregulate expression of Jag1 in response to cortical Wnt7, resulting in blunted activation of Notch signalling in NPC. Thus, Celsr3 and Fzd3 enable immature neurons to respond to Wnt7, upregulate Jag1 and thereby facilitate feedback signals that tune the timing of NPC fate decisions via Notch activation.

Date: 2016
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DOI: 10.1038/ncomms10936

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