Neurons are vulnerable to physical insults which compromise the integrity of both dendrites and axons. Unlike well characterized axon regeneration, our knowledge in dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used PVD neurons with stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After the primary dendrite was severed near the cell body, we observed a sprouting of new branches from the cut site within 3 hours. By 24 hours, the primary dendrite regrew to cover the original territory in complex pattern unlike the uninjured dendrites. We quantified the regeneration in broadly two aspects- the territory covered and fusion phenomena (Oren-Suissa et al.,2017, Kravtsov et al.,2017). Axon injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1(DLK-1) dependent regrowth from the severed end or conversion of neighboring dendrite to axon. However, Dendrite regeneration was independent of DLK-1 and other conventional axon regeneration pathways including cAMP elevation,
let-7 miRNA, Akt-1 and Phosphatidyl serine exposure/PS. Among various candidates tested,
ced-10 mutants showed a defect in dendrite regeneration. It is a RAC GTPase involved in regulation of neuronal cytoskeleton and cell engulfment. Cell-specific rescue experiments suggest that cell-autonomous and epidermal expression of CED-10 is required for dendrite regrowth and fusion, respectively. Moreover, the PVD-specific expression of an activated version of CED-10 led to both increased branching and fusion. We ventured further to find the upstream players which can control the function of RAC GTPase in dendrite regeneration. We found out that the TIAM-1 RhoGEF is required for dendrite regeneration and the activated CED-10 can bypass the requirement of TIAM-1 in dendrite regrowth. Our work provides a framework for understanding the cellular mechanism of dendrite regeneration using PVD model. Reference: Oren-Suissa, M., T. Gattegno, V. Kravtsov and B. Podbilewicz, 2017 Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans. Genetics 206: 215-230. Kravtsov, V., M. Oren-Suissa and B. Podbilewicz, 2017 The fusogen AFF-1 can rejuvenate the regenerative potential of adult dendritic trees by self-fusion. Development 144: 2364-2374.