Molecular Mechanisms of Neuronal Differentiation and Neural Circuit Formation
The mammalian brain is the most complex system in all of biology. The human brain has ~100 billion neurons and perhaps 500 trillion synapses, contact sites between neurons through which information flows. The differentiation of a vast array of distinct neuronal cell types from stem cell progenitors, and their migration to form layers and clusters, is a key developmental step that can be disrupted in human disorders such as microcephaly and lissencephaly. The elaboration of dendrites and axons and their formation of specific neural circuits underlies all mature function, and dysregulation of these processes underlies a wide variety of genetic and syndromic disorders, including forms of autism spectrum disorders, Down and Fragile X Syndromes, and schizophrenia. My laboratory is focused on identifying the fundamental molecular mechanisms that control neuronal differentiation and neural circuit formation during brain development. We take a candidate approach, generating allelic series of transgenic and knockout mice and analyzing their developmental phenotypes with a wide range of genetic, biochemical, pharmacological, molecular biology, and cell biology techniques. We focus on genes and processes that have been implicated in human neurodevelopmental disorders.