A cell-autonomous requirement for the cell cycle regulatory protein, Rb, in neuronal migration.
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.
Ferguson
Kerry L
KL
Ottawa Health Research Institute, University of Ottawa, Ottawa, Ontario, Canada.
McClellan
Kelly A
KA
Vanderluit
Jacqueline L
JL
McIntosh
William C
WC
Schuurmans
Carol
C
Polleux
Franck
F
Slack
Ruth S
RS
D000818:Animals; D017209:Apoptosis; D019521:Body Patterning; D064026:Calbindins; D002453:Cell Cycle; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D002470:Cell Survival; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D051379:Mice; D008953:Models, Anatomic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012175:Retinoblastoma / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors
D064026:Calbindins; D018398:Homeodomain Proteins; C121947:LHX6 protein, human; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D016160:Retinoblastoma Protein; D064030:S100 Calcium Binding Protein G; D014157:Transcription Factors