The branching of axons is a pivotal event in the development of neuronal circuitry and during the response of the nervous system to injury. We and others recently identified a crucial role for axonal mitochondria in axon branching. This proposal aims to advance the understanding of the role of mitochondria in axon branching and axonal physiology. The preliminary data unveil that nerve growth factor, a branch inducing signal, promotes the fission of axonal mitochondria which is in turn required for the ensuing branching. The PI3K signaling pathway is necessary and sufficient for the induction of fission by NGF.
Aim 1 of this proposal aims to determine whether neurotrophins which induce branching in vivo also induce fission and the role of fission in in vivo branching, and further dissect the signaling mechanism used by NGF to drive the fission of axonal mitochondria.
Aim 2 will address the role of the axonal cytoskeleton in the regulation of mitochondrial fission.
Aim 3 will seek to determine how the fission of mitochondria contributes to axonal physiology and the mechanism of axon branching. Collectively, these aims have the potential to make impactful advances which will be of interest to a wide community of scientists.
The branching of axons is a fundamental aspect of neurodevelopment and nervous system repair and plasticity. Mitochondria, important cellular organelles, were recently determined by us and others to have a necessary role in determining the sites and extent of branching. This proposal is based on the novel observation that NGF, a branch inducing factor, promotes the fission/division of axonal mitochondria which is in turn required for branching. The proposal aims to advance our understanding of the mechanism of branching in vivo and in vitro, the mechanism of mitochondria fission and determine how fission regulates the physiology of the axon.
| Smith, George M; Gallo, Gianluca (2018) The role of mitochondria in axon development and regeneration. Dev Neurobiol 78:221-237 |
| Nemani, Neeharika; Carvalho, Edmund; Tomar, Dhanendra et al. (2018) MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress. Cell Rep 23:1005-1019 |
| Smith, George; Gallo, Gianluca (2017) To mdivi-1 or not to mdivi-1: Is that the question? Dev Neurobiol 77:1260-1268 |
| Sainath, Rajiv; Armijo-Weingart, Lorena; Ketscheck, Andrea et al. (2017) Chondroitin sulfate proteoglycans negatively regulate the positioning of mitochondria and endoplasmic reticulum to distal axons. Dev Neurobiol 77:1351-1370 |
| Armijo-Weingart, Lorena; Gallo, Gianluca (2017) It takes a village to raise a branch: Cellular mechanisms of the initiation of axon collateral branches. Mol Cell Neurosci 84:36-47 |
