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; Andre M Goffinet

doi:10.1038/ncomms10936

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

Nat Commun. 2016 Mar 4:7:10936. doi: 10.1038/ncomms10936.

Authors

Wei Wang¹, Yves Jossin¹, Guoliang Chai¹, Wen-Hui Lien², Fadel Tissir¹, Andre M Goffinet^{1

3}

Affiliations

¹ Université catholique de Louvain, Institute of Neuroscience, 73 Avenue Mounier, Box B1.7316, 1200 Brussels, Belgium.
² Université catholique de Louvain, de Duve Institute, Avenue Hippocrate 74, Box B1.74.09, 1200 Brussels, Belgium.
³ WELBIO, 6 Avenue Pasteur, 1300 Wavre, Belgium.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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*
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism
Jagged-1 Protein
Membrane Proteins / genetics
Membrane Proteins / metabolism
Mice
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
Serrate-Jagged Proteins
Signal Transduction / physiology*
Staining and Labeling
Wnt Proteins / genetics
Wnt Proteins / metabolism*

Substances

Cadherins
Calcium-Binding Proteins
Celsr3 protein, mouse
Frizzled Receptors
Fzd3 protein, mouse
Intercellular Signaling Peptides and Proteins
Jag1 protein, mouse
Jagged-1 Protein
Membrane Proteins
Proto-Oncogene Proteins
Receptors, Cell Surface
Receptors, Notch
Serrate-Jagged Proteins
Wnt Proteins
Wnt7a protein, mouse
Wnt7b protein, mouse
Bromodeoxyuridine