The Role of Satb1 and Satb2 Genes in the Control of Neocortex Connectivity

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Satb2 is a transcription factor that controls cell type specific connectivity of neurons of the neocortex. Loss of Satb2 gene function in the mouse leads to multiple abnormalities in neocortical connectivity. Satb1 is the closest homologue of Satb2 and is also expressed in the developing neocortex, however its developmental function has not been characterized yet.In the previous funding period we characterized the interactions between the transcription factors Satb2 and Ctip2 and identified Unc5C and DCC as their targets. We also dissected their roles in the development of neocortical axonal tracts. Additionally we identified Ski as Satb2 co-factor in the developing neocortical neurons.The current project extension is designed to further characterize the genetic and molecular interactions between Satb2, Satb1 and Ski transcription factors in the control of cell type specific connectivity in the developing cortex. Another goal of the project is to identify molecular targets of these genes apart from Unc5C and DCC that contribute to the formation of cell type specific connectivity. This will be achieved by detailed analysis of Satb2, Satb1 and Ski conditional mutants and identification of down-stream targets of these genes by neocortical transcriptome Deep Sequencing and Chromatin Immunoprecipitation combined with genomic Deep Sequencing (ChIP-Seq). Identified targets will be analyzed functionally by means of in utero electroporation in order to validate their role in axonal pathfinding. Results of this project should provide insights into the molecular mechanisms underlying cell type specific axonal targeting of cortical neurons.