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| Subject Categories: Development | Neuroscience |
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| The EMBO Journal
(2005) 24, 4381–4391, doi:10.1038/sj.emboj.7600887 Published online 24 November 2005 |
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| A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration |
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| Kerry L Ferguson1, 4, Kelly A McClellan1, 4, Jacqueline L Vanderluit1, William C McIntosh1, Carol Schuurmans2, Franck Polleux3 and Ruth S Slack1 |
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1 Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada 2 Department of Biochemistry & Molecular Biology, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada 3 Department of Pharmacology, Neuroscience Center, University of North Carolina, Chapel Hill, NC, USA To whom correspondence should be addressed Ruth S Slack, Ottawa Health Research Institute, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5. Tel.: +1 613 562 5800; Fax: +1 613 562 5403; E-mail: rslack@uottawa.ca 4 These authors contributed equally to this work Received 25 April 2005; Accepted 3 November 2005; Published online 24 November 2005. |
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| Abstract |
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| Precise cell cycle regulation is critical for nervous system development. To assess the role of the cell cycle regulator, retinoblastoma (Rb) protein, in forebrain development, we studied mice with telencephalon-specific Rb deletions. We examined the role of Rb in neuronal specification and migration of diverse neuronal populations. Although layer specification occurred at the appropriate time in Rb mutants, migration of early-born cortical neurons was perturbed. Consistent with defects in radial migration, neuronal cell death in Rb mutants specifically affected Cajal–Retzius neurons. In the ventral telencephalon, although calbindin- and Lhx6-expressing cortical neurons were generated at embryonic day 12.5, their tangential migration into the neocortex was dramatically and specifically reduced in the mutant marginal zone. Cell transplantation assays revealed that defects in tangential migration arose owing to a cell-autonomous loss of Rb in migrating interneurons and not because of a defective cortical environment. These results revealed a cell-autonomous role for Rb in regulating the tangential migration of cortical interneurons. Taken together, we reveal a novel requirement for the cell cycle protein, Rb, in the regulation of neuronal migration. |
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| Keywords: cell cycle, neurogenesis, neuronal differentiation, retinoblastoma, tangential migration |
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