Connections between neurons are the substrate for nervous system function. The pattern of these connections within neural circuits is a key determinant of information flow through the system and therefore shapes behavioral output. Neurons are assembled into functional circuits during embryonic development, and when this wiring process goes awry, it can cause neural circuit dysfunction and disease. Hence, to understand the etiology of diseases that result from brain mis-wiring, including major neuropsychiatric illnesses such as autism spectrum disorder and schizophrenia, it is critical to elucidate the mechanisms that govern neural circuit development. Understanding these mechanisms not only promises to aid the diagnosis and treatment of neurodevelopmental disorders, but it also has the potential to inform therapeutic approaches aimed at repairing damaged neuronal connections after physical injury or onset of neurodegenerative disease.
The goal of the Jaworski lab is to understand how the nervous system is wired up during embryonic development. The guidance of nascent axons to their correct targets is an important aspect of brain wiring, and it is mediated by molecular cues that activate receptors on the leading process of the axon, the growth cone, to attract or repel axons. The mechanisms of axon pathfinding are still not completely defined, and our work focuses on several key questions about the logic of axon guidance. How do diverse types of neurons with vastly different cell lineage histories control the expression of common guidance receptors, and, conversely, how is combinatorial expression of multiple receptors regulated in a single neuronal population? How do growth cones integrate and filter information from multiple cues? What are the evolutionary mechanisms for adding and modifying axon guidance ligand-receptor signaling modules to allow the wiring of more complex nervous systems? We are addressing these questions using a multidisciplinary approach that integrates biochemical, bioinformatic, cell biological, embryological, and mouse genetic methods, and we incorporate cutting-edge experimental techniques, such as ex utero culture of mouse embryos, single-cell transcriptomics, and in toto imaging of the developing nervous system.
NIGMS/NIH - Institutional Development Award (RI-INBRE) (x2)
Brown University - Richard B. Salomon Faculty Research Award, OVPR Grant Resubmission Award, Seed Grant
Brown Institute for Brain Science - Innovation Award
Rhode Island Foundation - Medical Research Grant
DEARS Foundation - Project Grant (x2)
Brain Research Foundation - Fay/Frank Seed Grant
Whitehall Foundation - Research Grant
NINDS/NIH - R01
Rhode Island Neuroscience Consortium - New Frontiers Award