SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons

Neocortical projection neurons exhibit layer-specific molecular profiles and axonal connections. Here we show that the molecular identities of early-born subplate and deep-layer neurons are not acquired solely during generation or shortly thereafter but undergo progressive postmitotic refinement med...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-10, Vol.105 (41), p.16021-16026
Main Authors: Kwan, Kenneth Y, Lam, Mandy M.S, Krsnik, Željka, Kawasawa, Yuka Imamura, Lefebvre, Veronique, Šestan, Nenad
Format: Article
Language:English
Subjects:
Animals
Axons
Binding sites
Biological Sciences
Cell adhesion & migration
Cell Adhesion Molecules - genetics
Cell Differentiation
Cell Movement
Cell Surface Extensions
Cerebral cortex
DNA-Binding Proteins - genetics
Down regulation
Down-Regulation - genetics
Fezzes
Gene expression
Genotypes
Identity
Mice
Mice, Knockout
Mitosis
Molecular structure
Neocortex
Neocortex - cytology
Neurons
Neurons - cytology
Neuroscience
Proteins
Repressor Proteins - genetics
Rodents
SOXD Transcription Factors - physiology
Tumor Suppressor Proteins - genetics
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Summary:Neocortical projection neurons exhibit layer-specific molecular profiles and axonal connections. Here we show that the molecular identities of early-born subplate and deep-layer neurons are not acquired solely during generation or shortly thereafter but undergo progressive postmitotic refinement mediated by SOX5. Fezf2 and Bcl11b, transiently expressed in all subtypes of newly postmigratory early-born neurons, are subsequently downregulated in layer 6 and subplate neurons, thereby establishing their layer 5-enriched postnatal patterns. In Sox5-null mice, this downregulation is disrupted, and layer 6 and subplate neurons maintain an immature differentiation state, abnormally expressing these genes postnatally. Consistent with this disruption, SOX5 binds and represses a conserved enhancer near Fezf2. The Sox5-null neocortex exhibits failed preplate partition and laminar inversion of early-born neurons, loss of layer 5 subcerebral axons, and misrouting of subplate and layer 6 corticothalamic axons to the hypothalamus. Thus, SOX5 postmitotically regulates the migration, postmigratory differentiation, and subcortical projections of subplate and deep-layer neurons.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0806791105