The role of transcriptional coactivator ZMIZ1 in neocortical development
The successful generation of cellular diversity and circuit connectivity in the cerebral cortex is fundamental for high cognitive functioning in mammalian species. Disruptions to these processes are implicated in a range of neurodevelopmental disorders such as intellectual disability, autism spectrum disorders, schizophrenia, and other neuropsychiatric differences. Recent research has revealed transcriptional coregulator ZMIZ1 to be involved in a syndromic neurodevelopmental disorder in humans presenting with intellectual disability and other developmental delays. Although these disorders are known to be at least partially caused by disruptions in the cerebral cortex, the role of ZMIZ1 in the developing cortex is unknown. The objective of this study is to identify the potential roles of ZMIZ1 in the development of the neocortex, the portion of the cerebral cortex most responsible for the increased cellular diversity and cognitive function in primates and humans. We employ two Cre driver mouse lines to ablate the Zmiz1 gene broadly in the neocortex and specifically in corticothalamic projection neurons, which have been shown to upregulate Zmiz1, as compared to other projection neurons, during embryonic development. Using these mouse models, in combination with histological analysis, we identify potential roles for ZMIZ1 in the postnatal development of neocortical structure, and in the development of the corpus callosum, as mediated by midline closure and midline guidance structures. Together, our findings suggest that Zmiz1 is required in cortical progenitors for the successful assembly and wiring of the cerebral cortex.