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  Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex.

Silva, F. D., Zhang, K., Pinson, A., Fatti, E., Wilsch-Bräuninger, M., Herbst, J., et al. (2021). Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex. EMBO journal, The, 40(19): e108041. doi:10.15252/embj.2021108041.

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 Creators:
Silva, Fabio Da, Author
Zhang, Kaiqing, Author
Pinson, Anneline1, Author           
Fatti, Edoardo, Author
Wilsch-Bräuninger, Michaela1, Author           
Herbst, Jessica, Author
Vidal, Valerie, Author
Schedl, Andreas, Author
Huttner, Wieland1, Author           
Niehrs, Christof, Author
Affiliations:
1Max Planck Institute for Molecular Cell Biology and Genetics, Max Planck Society, ou_2340692              

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 Abstract: The role of WNT/β-catenin signalling in mouse neocortex development remains ambiguous. Most studies demonstrate that WNT/β-catenin regulates progenitor self-renewal but others suggest it can also promote differentiation. Here we explore the role of WNT/STOP signalling, which stabilizes proteins during G2/M by inhibiting glycogen synthase kinase (GSK3)-mediated protein degradation. We show that mice mutant for cyclin Y and cyclin Y-like 1 (Ccny/l1), key regulators of WNT/STOP signalling, display reduced neurogenesis in the developing neocortex. Specifically, basal progenitors, which exhibit delayed cell cycle progression, were drastically decreased. Ccny/l1-deficient apical progenitors show reduced asymmetric division due to an increase in apical-basal astral microtubules. We identify the neurogenic transcription factors Sox4 and Sox11 as direct GSK3 targets that are stabilized by WNT/STOP signalling in basal progenitors during mitosis and that promote neuron generation. Our work reveals that WNT/STOP signalling drives cortical neurogenesis and identifies mitosis as a critical phase for neural progenitor fate.

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 Dates: 2021-10-01
 Publication Status: Issued
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 Identifiers: DOI: 10.15252/embj.2021108041
Other: cbg-8168
PMID: 34431536
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Title: EMBO journal, The
  Other : EMBO J
Source Genre: Journal
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Pages: - Volume / Issue: 40 (19) Sequence Number: e108041 Start / End Page: - Identifier: -