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The laboratory investigates the cell biology of neuronal development, specifically the mechanisms of axon development. An emphasis of the laboratory is on understanding how extracellular signals regulate the axonal cytoskeleton (actin filaments and microtubules), and thus axon development. We are currently analyzing the mechanism of axon branch formation in response to neurotrophins, which are major determinants of axon development and serve to sculpt the final morphology of axons. The laboratory employs in vitro and in vivo approaches to manipulate and measure signaling pathways and the neuronal cytoskeleton. Through high resolution imaging we have been able to uncover novel aspects of the cytoskeletal and signaling mechanism of axon branching. We have found that localized microdomains of phosphoinositide 3-kinase (PI3K) signaling drive the formation of axonal actin filament patches, which in turn serve as the first step in the initiation of axon branches. Furthermore, we found that the induction of branches by nerve growth factor (NGF) requires the mitochondria-dependent axonal translation of mRNAs for cytoskeletal proteins involved in branching. Our current work aims to unveil how NGF signaling regulates the dynamics and function of axonal mitochondria and continue detailing the role of mitochondria in axon branching. Cells generate energy in the form ATP through mitochondrial respiration and glycolysis. A current additional research focus is on understanding how glycolysis, operative in embryonic axons, regulates axon morphogenesis. A separate line of research focuses on understanding how axons respond to physical injury, as occurs in spinal cord injury and traumatic brain injury, and how the physical injury is translated into disruption of the axonal cytoskeleton ultimately leading to axon severing and degeneration. By understanding the mechanisms of injury induced axon severing we aim to develop approaches for minimizing these events in the context of the injured adult nervous system. Finally, we are also addressing whether injury and signals that impair axon regeneration impact the function or dynamics of axonal mitochondria.
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NEURAL REGENERATION RESEARCHno. 10 (2024): 2109-2110
Molecular Neurobiologypp.1-19, (2024)
Journal of cell scienceno. 16 (2023)
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