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Elife. 2016 Jan 27;5:e09531. doi: 10.7554/eLife.09531.

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

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Institut de Biologie Valrose, University of Nice Sophia Antipolis, Nice, France.
Institut de Biologie Valrose, Institut national de la santé et de la recherche médicale, Nice, France.
Centre national de la recherche scientifique, Institut de Biologie Valrose, Nice, France.
Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, United States.
Laboratoire J.A. Dieudonné, Nice, France.


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.


Ctip2/Satb2 coexpression; Lmo4; cerebral cortex; developmental biology; epigenetic mechanism; layer V projection neurons; mouse; neuroscience; postnatal differentiation; stem cells

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