L1 cell adhesion molecules (L1CAMs) are conserved immunoglobulin-like transmembrane glycoproteins that have important roles in nervous system development through cell-to-cell adhesion. L1CAMs are integral to nervous system functioning and are involved in axon guidance, synaptic development, and synaptic function. Mutations of L1CAM genes are associated with disorders such as X-linked L1 syndrome. Siblings with the same L1CAM alleles can have different phenotypes, which suggests that modifier genes interact with L1CAM genes to contribute to symptoms. In contrast to mammalian model organisms, the genetic accessibility of the nematode C. elegans facilitates the characterization of such genetic interactions. C. elegans has a single gene, sax-7, which encodes the L1CAM orthologue with conserved structural protein motifs as well as neuronal functions as mammalian L1CAMs. Previously, a genetic interaction was identified between the L1CAM gene in C.elegans, sax-7, and genes that function in the synaptic vesicle cycle, revealing a role for L1 genes in modulating neurotransmission. For example, sax-7 genetically interacts with rab-3, which encodes a GTPase that targets synaptic vesicles to the presynaptic density; rab-3; sax-7 double mutant animals result in a synthetic uncoordinated (Unc) locomotion. A previous pilot genetic suppressor screen uncovered the role of the mitogen-activated protein kinase (MAPK) pathway in regulating locomotion. To better determine how sax-7 and MAPK regulate locomotion, I performed a screen to isolate additional genetic suppressors for rab-3;sax-7 locomotion defects using chemical mutagenesis. We will discuss the results of this screen as well as the implications of our findings to L1CAM-related human conditions.
This research was supported by the Undergraduate Research Opportunities Program (UROP).
Anderson, Emily E.
A C.elegans Screen for Genetic Supressors of L1CAMs with Uncoordinated Locomotion using Chemical Mutagenesis.
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