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.

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