Function of zinc finger protein 276 during CNS myelination and remyelination as part of the oligodendrocyte transcriptional network

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Proper formation of myelin sheaths is a prerequisite for fast saltatory conduction and maintenance of axonal integrity in the vertebrate nervous system. Two types of myelin-forming glia, namely Schwann cells in the PNS and oligodendrocytes in the CNS, are responsible for establishing this structure and their differentiation is regulated by distinct transcriptional regulatory networks. In this project I will study the role of the yet uncharacterized transcription factor zinc finger protein 276 (Zfp276) during myelination and remyelination within the CNS. I identified this factor in recent transcriptome and ChIP-Seq experiments as a potential target of Sox10, one of the key transcriptional regulators of myelination in both CNS and PNS. Using histological, immunohistochemical, and ultrastructural techniques, I will perform detailed phenotypic analyses on CNS tissue of mice that carry an oligodendrocyte-specific deletion of the Zfp276 gene. Changes in remyelination capacities upon loss or gain of Zfp276 function will be studied using the organotypic slice culture system. I will complement these in vivo studies with data from primary oligodendroglial cultures to identify molecular functions of Zfp276 during oligodendroglial differentiation. Expression profiling and analyses of genomic occupancy of Zfp276 will identify regulatory targets and signaling pathways that mediate its function during oligodendroglial differentiation. Comparative analyses of my sequencing data with published RNA-Seq and ChIP-Seq data sets for major regulators of CNS myelination, such as Sox10 and Olig2, will help to integrate Zfp276 into the oligodendroglial transcriptional network and to identify upstream regulators as well as functional interactors.