title: Protooncogene Ski cooperates with the chromatin-remodeling factor Satb2 in specifying callosal neurons.
abstract: First insights into the molecular programs orchestrating the progression from neural stem cells to cortical projection neurons are emerging. Loss of the transcriptional regulator Ski has been linked to the human 1p36 deletion syndrome, which includes central nervous system defects. Here, we report critical roles for Ski in the maintenance of the neural stem cell pool and the specification of callosal neurons. Ski-deficient callosal neurons lose their identity and ectopically express the transcription factor Ctip2. The misspecified callosal neurons largely fail to form the corpus callosum and instead redirect their axons toward subcortical targets. We identify the chromatin-remodeling factor Satb2 as a partner of Ski, and show that both proteins are required for transcriptional repression of Ctip2 in callosal neurons. We propose a model in which Satb2 recruits Ski to the Ctip2 locus, and Ski attracts histone deacetylases, thereby enabling the formation of a functional nucleosome remodeling and deacetylase repressor complex. Our findings establish a central role for Ski-Satb2 interactions in regulating transcriptional mechanisms of callosal neuron specification.
authors.affiliation: Institute of Physiology, Department of Biomedicine,  University of Basel, CH-4056 Basel,  Switzerland.
authors.forename: Constanze
authors.initials: C
authors.lastname: Baranek
authors.forename: Manuela
authors.initials: M
authors.lastname: Dittrich
authors.forename: Srinivas
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: Carine Gaiser
authors.initials: CG
authors.lastname: Bonnon
authors.forename: Olga
authors.initials: O
authors.lastname: Britanova
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Lanshakov
authors.forename: Fatiha
authors.initials: F
authors.lastname: Boukhtouche
authors.forename: Julia E
authors.initials: JE
authors.lastname: Sommer
authors.forename: Clemencia
authors.initials: C
authors.lastname: Colmenares
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.forename: Suzana
authors.initials: S
authors.lastname: Atanasoski
mesh_terms: D061085:Agenesis of Corpus Callosum / Q000196:embryology / Q000235:genetics / Q000473:pathology; D000818:Animals; D001369:Axons / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D003337:Corpus Callosum / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000378:metabolism; D036961:Matrix Attachment Region Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008957:Models, Genetic; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D025941:Protein Interaction Mapping; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C511143:Bcl11b protein, mouse; D004268:DNA-Binding Proteins; D036961:Matrix Attachment Region Binding Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D009707:Nucleosomes; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C501473:SATB2 protein, mouse; C512653:Ski protein, mouse; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D006655:Histone Deacetylases