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

• Published in: Nature communications 2016-03, Vol.7 (1), p.10936-10936, Article 10936
• Main Authors: Wang, Wei, Jossin, Yves, Chai, Guoliang, Lien, Wen-Hui, Tissir, Fadel, Goffinet, Andre M.
• Format: Article
• Language: English
• Subjects: 13/51; 14/19; 38/91; 631/208/737; 631/378/2571/1696; 631/378/2571/2579; 631/80/86; Animals; Bromodeoxyuridine; Cadherins - genetics; Cadherins - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cerebral Cortex - cytology; Cerebral Cortex - embryology; Female; Frizzled Receptors - genetics; Frizzled Receptors - metabolism; Gene Expression Regulation - physiology; Humanities and Social Sciences; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - metabolism; Jagged-1 Protein; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; multidisciplinary; Mutation; Neurogenesis - physiology; Pregnancy; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Notch - genetics; Receptors, Notch - metabolism; Science; Science (multidisciplinary); Serrate-Jagged Proteins; Signal Transduction - physiology; Staining and Labeling; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10936

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. The switch from neurogenesis to gliogenesis in cortical development is only partially understood. Here the authors show that Wnt-Planar cell polarity signaling in immature cortical neurons activates Notch in neural progenitor cells, thereby tuning the timing of their fate decisions.