| First Author | Da Silva F | Year | 2021 |
| Journal | EMBO J | Volume | 40 |
| Issue | 19 | Pages | e108041 |
| PubMed ID | 34431536 | Mgi Jnum | J:312371 |
| Mgi Id | MGI:6790012 | Doi | 10.15252/embj.2021108041 |
| Citation | Da Silva F, et al. (2021) Mitotic WNT signalling orchestrates neurogenesis in the developing neocortex. EMBO J 40(19):e108041 |
| abstractText | The role of WNT/beta-catenin signalling in mouse neocortex development remains ambiguous. Most studies demonstrate that WNT/beta-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. |
