Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex.
Pyramidal neurons of the neocortex can be subdivided into two major groups: deep- (DL) and upper-layer (UL) neurons. Here we report that the expression of the AT-rich DNA-binding protein Satb2 defines two subclasses of UL neurons: UL1 (Satb2 positive) and UL2 (Satb2 negative). In the absence of Satb2, UL1 neurons lose their identity and activate DL- and UL2-specific genetic programs. UL1 neurons in Satb2 mutants fail to migrate to superficial layers and do not contribute to the corpus callosum but to the corticospinal tract, which is normally populated by DL axons. Ctip2, a gene required for the formation of the corticospinal tract, is ectopically expressed in all UL1 neurons in the absence of Satb2. Satb2 protein interacts with the Ctip2 genomic region and controls chromatin remodeling at this locus. Satb2 therefore is required for the initiation of the UL1-specific genetic program and for the inactivation of DL- and UL2-specific genes.
Britanova
Olga
O
Max-Planck-Institute for Experimental Medicine, Hermann-Rein Strasse 3, 37075 Göttingen, Germany.
de Juan Romero
Camino
C
Cheung
Amanda
A
Kwan
Kenneth Y
KY
Schwark
Manuela
M
Gyorgy
Andrea
A
Vogel
Tanja
T
Akopov
Sergey
S
Mitkovski
Miso
M
Agoston
Denes
D
Sestan
Nenad
N
Molnár
Zoltán
Z
Tarabykin
Victor
V
D000818:Animals; D002232:Carbocyanines / Q000378:metabolism; D002454:Cell Differentiation; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D002232:Carbocyanines; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; C501473:SATB2 protein, mouse; D014157:Transcription Factors