Transcriptional regulation of cortical neuron migration by POU domain factors.
The identification of pathways mediated by the kinase Cdk5 and the ligand reelin has provided a conceptual framework for exploring the molecular mechanisms underlying proper lamination of the developing mammalian cerebral cortex. In this report, we identify a component of the regulation of Cdk5-mediated cortical lamination by genetic analysis of the roles of the class III POU domain transcription factors, Brn-1 and Brn-2, expressed during the development of the forebrain and coexpressed in most layer II-V cortical neurons. Brn-1 and Brn-2 appear to critically control the initiation of radial migration, redundantly regulating the cell-autonomous expression of the p35 and p39 regulatory subunits of Cdk5 in migrating cortical neurons, with Brn-1(-/-)/Brn-2(-/-) mice exhibiting cortical inversion.
McEvilly
Robert J
RJ
Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92037-0648, USA.
de Diaz
Marcela Ortiz
MO
Schonemann
Marcus D
MD
Hooshmand
Farideh
F
Rosenfeld
Michael G
MG
D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D018390:Gene Targeting; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018398:Homeodomain Proteins; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D050809:POU Domain Factors; D000091042:Reelin Protein; D012697:Serine Endopeptidases; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
C108298:Cdk5 activator p39; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D050809:POU Domain Factors; D000091042:Reelin Protein; D015534:Trans-Activators; D014157:Transcription Factors; C089495:neuronal Cdk5 activator (p25-p35); C085076:transcription factor Brn-2; C074065:Pou3f3 protein, mouse; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases