Article abstract
Nature Neuroscience 12, 735 - 744 (2009)
Published online: 17 May 2009 | doi:10.1038/nn.2339
Lfc and Tctex-1 regulate the genesis of neurons from cortical precursor cells
Andrée Gauthier-Fisher1,2,3,7, Dan C Lin1,2,7, Melissa Greeve4,5, David R Kaplan2,3, Robert Rottapel4,5 & Freda D Miller1,3,6
Abstract
The mechanisms that regulate symmetric, proliferative divisions versus asymmetric, neurogenic divisions of mammalian neural precursors are still not well understood. We found that Lfc (Arhgef2), a Rho-specific guanine nucleotide exchange factor that interacts with spindle microtubules, and its negative regulator Tctex-1 (Dynlt1) determine the genesis of neurons from precursors in the embryonic murine cortex. Specifically, genetic knockdown of Arhgef2 in cortical precursors either in culture or in vivo inhibited neurogenesis and maintained cells as cycling radial precursors. Conversely, genetic knockdown of Dynlt1 in radial precursors promoted neurogenesis and depleted cycling cortical precursors. Coincident silencing of these two genes indicated that Tctex-1 normally inhibits the genesis of neurons from radial precursors by antagonizing the proneurogenic actions of Lfc. Moreover, Lfc and Tctex-1 were required to determine the orientation of mitotic precursor cell divisions in vivo. Thus, Lfc and Tctex-1 interact to regulate cortical neurogenesis, potentially by regulating mitotic spindle orientation.
- Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
- Cell Biology Groups, Hospital for Sick Children, Toronto, Ontario, Canada.
- Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
- Ontario Cancer Institute, Toronto, Ontario, Canada.
- Departments of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
- Physiology, University of Toronto, Toronto, Ontario, Canada.
- These authors contributed equally to this work.
Correspondence to: Freda D Miller1,3,6 e-mail: fredam@sickkids.ca
