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A cell‐autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration
Author(s) -
Ferguson Kerry L,
McClellan Kelly A,
Vanderluit Jacqueline L,
McIntosh William C,
Schuurmans Carol,
Polleux Franck,
Slack Ruth S
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600887
Subject(s) - library science , political science , computer science
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.