| First Author | Rashidieh B | Year | 2021 |
| Journal | PLoS Genet | Volume | 17 |
| Issue | 10 | Pages | e1009334 |
| PubMed ID | 34710087 | Mgi Jnum | J:314161 |
| Mgi Id | MGI:6810413 | Doi | 10.1371/journal.pgen.1009334 |
| Citation | Rashidieh B, et al. (2021) Cep55 regulation of PI3K/Akt signaling is required for neocortical development and ciliogenesis. PLoS Genet 17(10):e1009334 |
| abstractText | Homozygous nonsense mutations in CEP55 are associated with several congenital malformations that lead to perinatal lethality suggesting that it plays a critical role in regulation of embryonic development. CEP55 has previously been studied as a crucial regulator of cytokinesis, predominantly in transformed cells, and its dysregulation is linked to carcinogenesis. However, its molecular functions during embryonic development in mammals require further investigation. We have generated a Cep55 knockout (Cep55-/-) mouse model which demonstrated preweaning lethality associated with a wide range of neural defects. Focusing our analysis on the neocortex, we show that Cep55-/- embryos exhibited depleted neural stem/progenitor cells in the ventricular zone as a result of significantly increased cellular apoptosis. Mechanistically, we demonstrated that Cep55-loss downregulates the pGsk3beta/beta-Catenin/Myc axis in an Akt-dependent manner. The elevated apoptosis of neural stem/progenitors was recapitulated using Cep55-deficient human cerebral organoids and we could rescue the phenotype by inhibiting active Gsk3beta. Additionally, we show that Cep55-loss leads to a significant reduction of ciliated cells, highlighting a novel role in regulating ciliogenesis. Collectively, our findings demonstrate a critical role of Cep55 during brain development and provide mechanistic insights that may have important implications for genetic syndromes associated with Cep55-loss. |
