Scientific article
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English

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

Published ineLife, vol. 5, e09531
Publication date2016
Abstract

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features.

Keywords
  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Epigenesis, Genetic
  • Gene Expression Regulation, Developmental
  • LIM Domain Proteins/metabolism
  • Matrix Attachment Region Binding Proteins/analysis
  • Mice
  • Neurons/physiology
  • Repressor Proteins/analysis
  • Somatosensory Cortex/embryology
  • Transcription Factors/analysis
  • Tumor Suppressor Proteins/analysis
Citation (ISO format)
HARB, Kawssar et al. Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications. In: eLife, 2016, vol. 5, p. e09531. doi: 10.7554/elife.09531
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Article (Published version)
Identifiers
Journal ISSN2050-084X
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257downloads

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