RESEARCH

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 networks during embryonic development, and when this wiring process goes awry, it can cause neural circuit dysfunction and disease.

The goal of the Jaworski lab is to understand how the nervous system is wired up during embryogenesis. 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 aims to identify the relevant molecules and signaling pathways, focusing on several key questions about the logic of axon guidance. How do neurons control and coordinate the expression of axon guidance receptors? 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.

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Our work to elucidate mechanisms of neural circuit development can aid the diagnosis and treatment of neurodevelopmental disorders. It also has the potential to inform therapeutic approaches aimed at repairing damaged neuronal connections after physical injury or onset of neurodegenerative disease.