Development and repair of neural circuit in C. elegans
Axon specification: Regulation of microtubule (MT) dynamics is a critical step in axon specification and regeneration. We are using the mechanosensory neuron, namely Posterior Lateral Microtubule (PLM) to identify the regulators of MT dynamics in neurons. We found that kinesin-13 family MT depolymerizing factor KLP-7 is required for proper establishment neuronal polarity (Puri et al 2019; Puri et al 2021). Using the klp7 mutant background, we have conducted a genetic screening and identified mutations in novel regulators. Fine regulation of the MT cytoskeleton has clinical relevance because mutations in human MT associated proteins cause a wide range of neurodegenerative disorders. Axon Regeneration: Traumatic injury in the nervous system leads to devastating consequences such as paralysis. The regenerative capacity of the nervous system is limited in adulthood. Using the finely focused lasers of the 2-photon microscope, we can sever the neurons across the depth of the worm body. We are studying the molecular basis of axon regrowth and addressing the functional consequences of regeneration using behavioral assays. We have discovered that a self-fusion of injured proximal and distal end leads to rapid functional repair (Basu et al 2017). We further found that proper targeting and synapse formation of an injured axon is controlled by Insulin signaling (IIS) (Basu et al 2021). Finally, we have shown recently that axon regeneration can be enhanced by physical exercise (Kumar et al 2021) Dendrite Regeneration: We have recently established the PVD neuron of the worm as a model for studying the mechanism of dendrite regeneration (Brar et al 2022). Overall, our work help inform therapeutic strategies for the treatment of nervous system injuries in humans. Laser Neurosurgery at NBRC, Credits: Atrayee Basu and Shirshendu Dey |
Axotomy of PLM neurons on both right and left sides
Loss of posterior touch sensation following axotomy of both PLMs
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