[en] BACKGROUND: During the development of the mammalian cerebral cortex, newborn postmitotic projection neurons are born from local neural stem cells and must undergo radial migration so as to position themselves appropriately to form functional neural circuits. The zinc finger transcriptional repressor Rp58 (also known as Znf238 or Zbtb18) is critical for coordinating corticogenesis, but its underlying molecular mechanism remains to be better characterised. FINDINGS: Here, we demonstrate that the co-expression of Rp58 and the cyclin dependent kinase inhibitor (CDKI) p27(kip1) is important for E14.5-born cortical neurons to coordinate cell cycle exit and initiate their radial migration. Notably, we find that the impaired radial positioning of Rp58-deficient cortical neurons within the embryonic (E17.5) mouse cortex, as well as their multipolar to bipolar transition from the intermediate zone to the cortical plate can be restored by forced expression of p27(kip1) in concert with suppression of Rnd2, a downstream target gene of Rp58. Furthermore, the restorative effects of p27(kip1) and Rnd2 abrogation are reminiscent of suppressing RhoA signalling in Rp58-deficient cells. CONCLUSIONS: Our findings demonstrate functional interplay between a transcriptional regulator and a CDKI to mediate neuroprogenitor cell cycle exit, as well as to promote radial migration through a molecular mechanism consistent with suppression of RhoA signalling.
Disciplines :
Genetics & genetic processes
Author, co-author :
Clement, Olivier
Hemming, Isabel Anne
Gladwyn-Ng, Ivan ; Université de Liège - ULiège > Giga - Neurosciences
Qu, Zhengdong
Li, Shan Shan
Piper, Michael
Heng, Julian Ik-Tsen
Language :
English
Title :
Rp58 and p27(kip1) coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex.
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