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Neural Dev. 2017 May 15;12(1):8. doi: 10.1186/s13064-017-0084-3.

Rp58 and p27kip1 coordinate cell cycle exit and neuronal migration within the embryonic mouse cerebral cortex.

Author information

1
The Harry Perkins Institute of Medical Research, Perth, WA, 6009, Australia.
2
The Centre for Medical Research, University of Western Australia, Perth, WA, 6009, Australia.
3
EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia.
4
The School of Biomedical Sciences, University of Queensland, Brisbane, 4072, Australia.
5
Queensland Brain Institute, University of Queensland, Brisbane, 4072, Australia.
6
The Harry Perkins Institute of Medical Research, Perth, WA, 6009, Australia. Julian.Heng@curtin.edu.au.
7
The Centre for Medical Research, University of Western Australia, Perth, WA, 6009, Australia. Julian.Heng@curtin.edu.au.
8
EMBL Australia, The Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia. Julian.Heng@curtin.edu.au.
9
Curtin Health Innovation Research Institute, Curtin University, Bentley, 6845, Australia. Julian.Heng@curtin.edu.au.

Abstract

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) p27kip1 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 p27kip1 in concert with suppression of Rnd2, a downstream target gene of Rp58. Furthermore, the restorative effects of p27kip1 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.

KEYWORDS:

Cerebral Cortex; Neurodevelopment; Neurogenesis; Neuronal morphology; Radial migration; Transcription Factor

PMID:
28506232
PMCID:
PMC5433244
DOI:
10.1186/s13064-017-0084-3
[Indexed for MEDLINE]
Free PMC Article

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