Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis

Gaëlle Friocourt, Shigeaki Kanatani, Hidenori Tabata, Masato Yozu, Takao Takahashi, Mary Antypa, Odile Raguénès, Jamel Chelly, Claude Férec, Kazunori Nakajima, John G. Parnavelas

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89 Citations (Scopus)

Abstract

The aristaless-related homeobox (ARX) gene has been implicated in a wide spectrum of disorders ranging from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. To better understand its role in corticogenesis, we used in utero electroporation to knock down or overexpress ARX. We show here that targeted inhibition of ARX causes cortical progenitor cells to exit the cell cycle prematurely and impairs their migration toward the cortical plate. In contrast, ARX overexpression increases the length of the cell cycle. In addition, we report that RNA interferencemediated inactivation of ARX prevents cells from acquiring multipolar morphology in the subventricular and intermediate zones, resulting in decreased neuronal motility. In contrast, ARX overexpression appears to promote the development of tangentially oriented processes of cells in the subventricular and intermediate zones and affects radial migration of pyramidal neurons. We also demonstrate that the level of ARX expression is important for tangential migration of GABA-containing interneurons, because both inactivation and overexpression of the gene impair their migration from the ganglionic eminence. However, our data suggest that ARX is not directly involved in GABAergic cell fate specification. Overall, these results identify multiple and distinct cell-autonomous roles for ARX in corticogenesis.

Original languageEnglish
Pages (from-to)5794-5805
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number22
DOIs
Publication statusPublished - 2008 May 28

Keywords

  • ARX
  • Cell cycle
  • Interneuron
  • Lissencephaly
  • Neuronal migration
  • RNA interference

ASJC Scopus subject areas

  • Neuroscience(all)

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    Friocourt, G., Kanatani, S., Tabata, H., Yozu, M., Takahashi, T., Antypa, M., Raguénès, O., Chelly, J., Férec, C., Nakajima, K., & Parnavelas, J. G. (2008). Cell-autonomous roles of ARX in cell proliferation and neuronal migration during corticogenesis. Journal of Neuroscience, 28(22), 5794-5805. https://doi.org/10.1523/JNEUROSCI.1067-08.2008