Brar, H. K. | bioRxiv Science

bioRxiv2023

Functional recovery associated with dendrite regeneration in PVD neuron of C. elegans

PVD neuron of C. elegans is a highly polarized cell with well-defined axonal, and dendritic compartments. PVD neuron operates in multiple sensory modalities controlling both nociceptive touch sensation and body posture. Although both axon and dendrites of this neuron show regeneration response following laser-assisted injury, it is rather unclear how the behavior associated with this neuron is affected by the loss of these structures. It is also unclear whether neurite regrowth would lead to functional restoration in these neurons. Upon axotomy, using a femtosecond laser, we saw that harsh touch response was specifically affected leaving the body posture unperturbed. Subsequently, recovery in the touch response is highly correlated to the axon regrowth, which was dependent on DLK-1 MAP Kinase. Dendrotomy of both major and minor primary dendrites affected the wavelength and amplitude of sinusoidal movement without any apparent effect on harsh touch response. We further correlated the recovery in posture behavior to the type of dendrite regeneration events. We found that dendrite regeneration with the fusion and reconnection between the proximal and distal branches of the injured dendrite corresponded to improved recovery of posture. Our data revealed that the axons and dendrites differentially regulate the functions of PVD neurons. It also revealed that dendrite and axon regeneration are both functionally and molecularly distinct.

neuroscience↗

bioRxiv2021

Dendrite regeneration in C. elegans is controlled by the RAC GTPase CED-10 and the RhoGEF TIAM-1

Neurons are vulnerable to physical insults which compromise the integrity of both dendrites and axons. Although several molecular pathways of axon regeneration are identified, our knowledge of dendrite regeneration is limited. To understand the mechanisms of dendrite regeneration, we used PVD neurons in C. elegans having stereotyped branched dendrites. Using femtosecond laser, we severed the primary dendrites and axon of this neuron. After severing the primary dendrites near the cell body, we observed sprouting of new branches from the proximal site within 6 hours, which regrew further with timein an unstereotyped manner.This was accompanied by reconnection between the proximal and distal dendrites as well as the fusion among the higher-order branches as reported before. We quantified the regeneration pattern in threeaspects -territory length, number of branchesand fusion phenomena.Axonal injury causes a retraction of the severed end followed by a Dual leucine zipper kinase-1 (DLK-1) dependent regrowth from the severed end.We tested the roles of the major axon regenerationsignaling hubs such as DLK-1-RPM-1, cAMP elevation, let-7 miRNA, AKT-1, Phosphatidyl serine exposure/PS in dendrite regeneration. We found that neither regrowth nor fusionis affected by the axon injury pathway molecules. Surprisingly, we found that the RAC GTPase CED-10and its upstream GEF TIAM-1 play a cell-autonomous role in dendrite regeneration. Additionally, function of CED-10 in epidermal cell is critical for post-dendrotomy fusion phenomena. This work describes a novel regulatory mechanism of dendrite regeneration andprovides a framework for understanding the cellular mechanism of dendrite regeneration using PVD neuron as a model system.

neuroscience↗