title: Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications.
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.
authors.affiliation: 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.
authors.forename: Kawssar
authors.initials: K
authors.lastname: Harb
authors.affiliation: 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.
authors.forename: Elia
authors.initials: E
authors.lastname: Magrinelli
authors.affiliation: 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.
authors.forename: Céline S
authors.initials: CS
authors.lastname: Nicolas
authors.affiliation: 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.
authors.forename: Nikita
authors.initials: N
authors.lastname: Lukianets
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Frangeul
authors.affiliation: 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.
authors.forename: Mariel
authors.initials: M
authors.lastname: Pietri
authors.affiliation: Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, United States.
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sandoz
authors.affiliation: Institut de Biologie Valrose, University of Nice Sophia Antipolis, Nice, France.|Laboratoire J.A. Dieudonné, Nice, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Grammont
authors.affiliation: Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Jabaudon
authors.affiliation: 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.
authors.forename: Michele
authors.initials: M
authors.lastname: Studer
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Alfano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D060588:LIM Domain Proteins / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000032:analysis; D051379:Mice; D009474:Neurons / Q000502:physiology*; D012097:Repressor Proteins / Q000032:analysis; D013003:Somatosensory Cortex / Q000196:embryology*; D014157:Transcription Factors / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C511143:Bcl11b protein, mouse; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D036961:Matrix Attachment Region Binding Proteins; D012097:Repressor Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Ctip2/Satb2 coexpression; Lmo4; cerebral cortex; developmental biology; epigenetic mechanism; layer V projection neurons; mouse; neuroscience; postnatal differentiation; stem cells
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