Postmitotic regulation of sensory area patterning in the mammalian neocortex by Lhx2

Current knowledge suggests that cortical sensory area identity is controlled by transcription factors (TFs) that specify area features in progenitor cells and subsequently their progeny in a one-step process. However, how neurons acquire and maintain these features is unclear. We have used condition...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-05, Vol.112 (21), p.6736-6741
Main Authors: Zembrzycki, Andreas, Perez-Garcia, Carlos G., Wang, Chia-Fang, Chou, Shen-Ju, O’Leary, Dennis D. M.
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Body Patterning - genetics
Body Patterning - physiology
Brain
Cell division
Epigenesis, Genetic
Genes
LIM-Homeodomain Proteins - deficiency
LIM-Homeodomain Proteins - genetics
LIM-Homeodomain Proteins - physiology
Mammals
Mice
Mice, Knockout
Mitosis
Models, Neurological
Neocortex - cytology
Neocortex - growth & development
Neocortex - physiology
Neural Pathways - cytology
Neural Pathways - growth & development
Neural Pathways - physiology
Neurons
Neurons - cytology
Neurons - physiology
Sensory perception
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - physiology
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Summary:Current knowledge suggests that cortical sensory area identity is controlled by transcription factors (TFs) that specify area features in progenitor cells and subsequently their progeny in a one-step process. However, how neurons acquire and maintain these features is unclear. We have used conditional inactivation restricted to postmitotic cortical neurons in mice to investigate the role of the TF LIM homeobox 2 (Lhx2) in this process and report that in conditional mutant cortices area patterning is normal in progenitors but strongly affected in cortical plate (CP) neurons. We show thatLhx2controls neocortical area patterning by regulating downstream genetic and epigenetic regulators that drive the acquisition of molecular properties in CP neurons. Our results question a strict hierarchy in which progenitors dominate area identity, suggesting a novel and more comprehensive two-step model of area patterning: In progenitors, patterning TFs prespecify sensory area blueprints. Sequentially, sustained function of alignment TFs, includingLhx2, is essential to maintain and to translate the blueprints into functional sensory area properties in cortical neurons postmitotically. Our results reemphasize critical roles forLhx2that acts as one of the terminal selector genes in controlling principal properties of neurons.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1424440112