Cooperation of Transcription Factor PAX6 with Chromatin-Remodeling Complex BAF During Embryonic Development in Mammals

The transcription factor Pax6, a member of the Pax family class IV, is a key regulator of multiple developmental processes. These include brain patterning, neuronal specification, migration, maturation, and axonal guidance, all of which are essential for the formation of proper neuronal networks. In the mammalian brain, Pax6 exhibits region-specific expression throughout the entire lifespan. During early embryogenesis, the chromatin remodeling BAF complex cooperates with Pax6 to direct cell differentiation along the neuroectodermal pathway. This partnership regulates the development of neurons from ventricular radial glia, the formation of primordia, the regionalization of the cerebral cortex, and even adult neurogenesis. Given the crucial role of chromatin regulation in neocortical neurogenesis, it is notable that mutations in chromatin modifiers like the BAF complex - a multi-subunit mammalian homolog of the yeast SWI/SNF complex - are often linked to neurodevelopmental disorders. In humans, disruption of PAX6 function leads to the congenital aniridia and several other phenotypes, primarily known for affecting eye development. This review covers findings from animal model studies, which establish PAX6 as a master regulator of central nervous system embryogenesis, and clinical data from patients with PAX6 insufficiency. The focus is on elucidating the role of PAX6 in neurological disorders and its functional interplay with chromatin remodeling complexes.