The molecular logic of neuronal generation, placement, and connectivity provides the framework for the emergence of functional neuronal connectome in the brain. Our current goal is to understand the cellular and molecular mechanisms underlying the generation and appropriate allocation of distinct classes of neurons in the mammalian cerebral cortex and the relevance of these mechanisms to neurodevelopmental disorders.
We combine in vivo examination of embryonic cortical development with genetic analysis of progenitor development, neurogenesis, neuron- glial interactions, and neuronal differentiation to understanding the mechanisims underlying the generation, placement and connectivity of diverse groups of neurons in cerebral cortex. Towards this goal, we are studying the following three related questions using multidisciplinary approaches:
1) What are the signals that regulate the establishment, development and differentiation of different cortical progenitors necessary for neurogenesis and oriented neuronal migration in cerebral cortex?
2) How do neurons reach their target areal locations, coalesce into distinct layers, and form functional circuits in the developing cerebral cortex?
3) How do human genomic changes associated with neurodevelopmental disorders such as autism spectrum disorders, schizophrenia, and ciliopathies affect the generation, placement and connectivity of neurons?
This multidisciplinary effort provides a framework to characterize the developmental mechanisms that guide the emergence of cerebral cortical organization and connectivity. An understanding of these mechanisms and how they are altered in models of neurodevelopmental disorders will help delineate the pathophysiological processes that underly neurodevelopmental disorders.