Understanding the mechanisms that govern neuronal wiring is a central focus of developmental neurobiology and, importantly, will result in the identification of molecular mechanisms relevant to many disease processes. The overarching goal of our research is to better understand how molecular cues regulate neuronal morphogenesis, synapse development and refinement, which lead to the proper wiring of the nervous system that ultimately result in the execution of complex behavior in the organism.
The elaborate and precise patterns of neuronal connections in the mammalian central nervous system (CNS) and peripheral nervous system (PNS) established during development depend critically upon a vast number of extrinsic molecular cues. Neurons form connections with their appropriate targets by extending processes called axons and dendrites, which ultimately shape their diverse morphologies. The establishment of neuronal morphology is crucial for proper neural circuit formation, which enable complex behavior and cognitive function. However, the mechanisms by which axons select their correct pathways, find their targets, and form proper synaptic connections is not clearly understood. Furthermore, the identity and mechanisms that enables molecular cues to control the development of neuronal morphology and synaptic connections, which collectively comprise the neural circuitry underlying complex cognitive function is poorly understood. Moreover, the wiring of neuronal circuits requires the precise formation and subsequent refinement of synapses during postnatal development. The majority of excitatory synapses in the mammalian CNS are formed on dendritic spines, tiny protrusions extended from the dendritic membrane. The morphology of the dendritic arbor and distribution of spines are critical determinants of correct circuit function. However, little is known about the molecules that restrain the number of dendritic spines and prune synapses.
Research questions and approaches
Accordingly, our research team is interested in the following questions: 1) what are the molecules controlling neural circuit formation? 2) how are these connections maintained throughout life? and 3) what are the underlying cellular and molecular mechanims controlling axonal guidance versus dendrite/synapse formation? To address these questions, we will employ cellular, molecular, and genetic approaches to analyze both the central and peripheral arms of the mouse nervous system. We will use a combination of interdisciplinary approaches including, but not limited to, sophisticated mouse genetics (inducible knockout/knockin, CRISPR) to perform in vitro and in vivo experiments, and physiology and behavioral analysis to provide a platform to study complex neural circuits formation and how defects in salient connections may lead to the development of neurological disorders, such as autism spectrum disorder.