A Novel Role for Notch in Neuronal Connectivity in C. Elegans
Notch receptors are conserved transmembrane proteins that regulate key developmental processes and promote stem cell proliferation and renewal. Defects in the Notch pathway are especially evident in neurons, where Notch signaling remains active in the nervous system from birth to adulthood. These receptors are highly conserved across many species, including humans, and have been highly described in the model organism Caenorhabditis elegans. In our research, we documented the development of light touch sensing mechanosensory neurons at the nerve ring in C. elegans. We first observed that sup-17/ADAM10 animals, a Notch pathway mutant, had significantly higher rates of ALM-AVM nerve ring breakage than wild type animals. This observation lead us to test other Notch mutants to determine if the pathway was involved. Multiple different Notch pathway mutants were crossed with animals with an integrated transgene that expresses GFP in mechanosensory neurons (zdIs5) to visualize their nerve rings. Significantly higher rates of breakage were found in all Notch mutant animals when compared to wild type, which suggests that the Notch pathway is involved in ALM-AVM nerve ring development. Genetically identical Notch mutants did not exhibit different break rates across life stages. Therefore, the defect is likely to be developmental rather than degeneration or a developmental delay as would have been indicated by increases or decreases in break rates across time respectively. We next need to identify which cells Notch works through to promote ALM-AVM nerve ring development. To do so, we are currently performing tissue specific rescue experiments for both the mechanosensory neurons and the surrounding glia. We are also in the process of determining if the defect effects the normal behavior of the worm using a light activated protein called channelrhodopsin. By expressing this protein in the animals’ light touch sensing mechanosensory neurons, we can use blue light to control the activation of ALM and AVM neurons and make powerful conclusions about any behavioral differences in Notch mutant animals.