Mutual regulation between Satb2 and Fezf2 promotes subcerebral projection neuron identity in the developing cerebral cortex.
Generation of distinct cortical projection neuron subtypes during development relies in part on repression of alternative neuron identities. It was reported that the special AT-rich sequence-binding protein 2 (Satb2) is required for proper development of callosal neuron identity and represses expression of genes that are essential for subcerebral axon development. Surprisingly, Satb2 has recently been shown to be necessary for subcerebral axon development. Here, we unravel a previously unidentified mechanism underlying this paradox. We show that SATB2 directly activates transcription of forebrain embryonic zinc finger 2 (Fezf2) and SRY-box 5 (Sox5), genes essential for subcerebral neuron development. We find that the mutual regulation between Satb2 and Fezf2 enables Satb2 to promote subcerebral neuron identity in layer 5 neurons, and to repress subcerebral characters in callosal neurons. Thus, Satb2 promotes the development of callosal and subcerebral neurons in a cell context-dependent manner.
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064;
William L
WL
McKenna
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064;
Christian F
CF
Ortiz-Londono
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064;
Thomas K
TK
Mathew
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064;
Kendy
K
Hoang
Department of Bioengineering, University of California, Santa Cruz, CA 95064.
Sol
S
Katzman
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, CA 95064; bchen@ucsc.edu.
Bin
B
Chen
D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism; D001665:Binding Sites; D001931:Brain Mapping; D019070:Cell Lineage; D002540:Cerebral Cortex / Q000196:embryology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D036961:Matrix Attachment Region Binding Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016548:Prosencephalon / Q000196:embryology; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C501473:SATB2 protein, mouse; D014157:Transcription Factors; C412364:Zfp312 protein, mouse
Fezf2; Satb2; cell fate; cerebral cortex; subcerebral neurons