Regulation of cerebral cortex development by alternative splicing factor TRA2B.

摘要

The cerebral cortex is the region of the brain where conscious perceptions are integrated to form thoughts and decisions. Development of the appropriate cells and connections to make this possible is achieved through a complex system of regulation. Alternative splicing of nascent transcripts is involved in regulation of many of components of cerebral cortex development including cell-fate decisions and cell migration. In effort to explain how these crucial splicing events are regulated, splicing factors with functional roles in brain development have been identified. This dissertation focuses on the role of TRA2B in Mus musculus cerebral cortex development. TRA2B is an SR-related splicing factor known to be important in regulating developmental processes and disease severity. Our study found that TRA2B is expressed in cortical progenitor cells and cortical neurons from the onset of neurogenesis. Examination of a cortex-specific TRA2B knockout mouse showed that loss of TRA2B resulted in a postnatal cerebral cortex reduced in size and organization, with fewer cortical axonal projections. Further observations found that TRA2B is required for the survival of cerebral cortex progenitors, which at least partially explains the observed postnatal phenotype. Further experiments are required to more precisely define the role of TRA2B in cerebral cortex development.