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PMID: 22892427 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

POU-III transcription factors (Brn1, Brn2, and Oct6) influence neurogenesis, molecular identity, and migratory destination of upper-layer cells of the cerebral cortex.

Cerebral cortex (New York, N.Y. : 1991) ·Vol. 23 ·No. 11 ·2013-11-00 ·Pages 2632-43

Dominguez MH, Ayoub AE, Rakic P

Abstract

The upper layers (II-IV) are the most prominent distinguishing feature of mammalian neocortex compared with avian or reptilian dorsal cortex, and are vastly expanded in primates. Although the time-dependent embryonic generation of upper-layer cells is genetically instructed within their parental progenitors, mechanisms governing cell-intrinsic fate transitions remain obscure. POU-homeodomain transcription factors Pou3f3 and Pou3f2 (Brn1 and Brn2) are known to label postmitotic upper-layer cells, and are redundantly required for their production. We find that the onset of Pou3f3/2 expression actually occurs in ventricular zone (VZ) progenitors, and that Pou3f3/2 subsequently label neural progeny switching from deep-layer Ctip2(+) identity to Satb2(+) upper-layer fate as they migrate to proper superficial positions. By using an Engrailed dominant-negative repressor, we show that sustained neurogenesis after the deep- to upper-layer transition requires the proneual action of Pou3fs in VZ progenitors. Conversely, single-gene overexpression of any Pou3f in early neural progenitors is sufficient to specify the precocious birth of Satb2(+) daughter neurons that extend axons to the contralateral hemisphere, as well as exhibit robust pia-directed migration that is characteristic of upper-layer cells. Finally, we demonstrate that Pou3fs influence multiple stages of neurogenesis by suppressing Notch effector Hes5, and promoting the expression of proneural transcription factors Tbr2 and Tbr1.

Keywords
In utero electroporation Neurogenesis Upper layer development differentiation
MeSH Terms
Animals Basic Helix-Loop-Helix Transcription Factors/metabolism Carrier Proteins/metabolism Cell Cycle Proteins/metabolism Cell Movement Cerebral Cortex/cytology,embryology,metabolism Macaca mulatta Matrix Attachment Region Binding Proteins/metabolism Mice Nerve Tissue Proteins/metabolism Neurogenesis Neurons/metabolism Octamer Transcription Factor-6/metabolism POU Domain Factors/metabolism Repressor Proteins/metabolism Transcription Factors/metabolism
Chemicals
Basic Helix-Loop-Helix Transcription Factors Carrier Proteins Cell Cycle Proteins CtIP protein, mouse Hes5 protein, mouse Matrix Attachment Region Binding Proteins Nerve Tissue Proteins POU Domain Factors Repressor Proteins SATB2 protein, mouse Transcription Factors Octamer Transcription Factor-6 Pou3f3 protein, mouse Pou3f2 protein, mouse
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dominguez Martin H
Department of Neurobiology, Yale University School of Medicine and Kavli Institute for Neuroscience, 06510 New Haven, CT, USA.
Ayoub Albert E
Rakic Pasko
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Article Info
Journal
Cerebral cortex (New York, N.Y. : 1991)
Abbr.
Cereb Cortex
ISSN
1460-2199
DOI
10.1093/cercor/bhs252
Published
2013-11-00
Epub
2012-00-14
Pages
2632-43
Language
English
Region
United States
NLM ID
9110718
PMCID
PMC3792741
Subset
IM
Grants
NINDS NIH HHS · R01 NS014841 · United States
NINDS NIH HHS · R01-NS038296 · United States
NIDA NIH HHS · R37 DA023999 · United States
NIDA NIH HHS · R01-DA023999 · United States
NINDS NIH HHS · R01 NS038296 · United States
External Links
PubMed source DOI: 10.1093/cercor/bhs252 PMC Full Text View journal details
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