Using C. elegans as a Model to Understand How sax-7 Effects Canal-Associated Neurons
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Using C. elegans as a Model to Understand How sax-7 Effects Canal-Associated Neurons
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2021
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L1CAMs are transmembrane glycoproteins of the immunoglobulin (Ig) superfamily that are encoded by the L1 gene. These proteins play important roles in nervous system development that include neuronal migration and axon migration. Consistent with the importance of L1CAMs in nervous system development, mutations to the L1 gene can result in L1 syndrome, which emcompases neurological disorders including hydrocephalus, a life threatening disease characterized by cerebrospinal fluid buildup within the ventricles of the brain. Currently it is a mystery how impaired L1 function causes hydrocephalus. Interestingly, siblings with L1 syndrome carrying the identical mutant allele can differ in whether or not they have hydrocephalus (Jouet et al. 1995; Schrander-Stumpel et al. 1995; Fransen et al. 1998), suggesting the presence of genetic modifiers. Thus, we hypothesize that the L1 gene acts synergistically with other genes for enhancement of disease expression. To better understand the manifestation of hydrocephalus in L1 patients, L1 interacting genes must be identified. To do so, we use the genetic model organism, Caenorhabditis. elegans to study L1 and identify L1-interacting genes. Canonical L1CAMs are conserved in C. elegans and are encoded by the sax-7 gene. Like mammalian L1, sax-7 functions in the development and maintenance of the nervous system. Due to defects in maintaining neural architecture, loss of sax-7 (sax7(0)) results in progressive displacement of neuronal cell bodies and axons. Recently, preliminary studies in the Chen lab uncovered a genetic interaction between sax-7 and Ras in C. elegans. Ras(gf) in a sax-7(0) mutant results in synthetic lethality caused by fluid buildup in the animal. Ras(gf) in humans is known to cause a set of congenital diseases collectively termed Rasopathies which most interestingly includes variable hydrocephalus. Additionally, the Chen lab determined that the conditional knockout (KO) of sax-7 in the nervous system is sufficient to result in similar progressive fluid accumulation in Ras(gf) animals. These results point to a role for SAX-7 specifically in neurons in regulating fluid homeostasis. Of the 302 neurons that are present in C. elegans, only two are documented to function in fluid regulation. These two neurons, known as the Canal-associated neurons (CANs) are necessary for fluid homeostasis; loss of CANs results in lethality caused by fluid accumulation within the pseudocoelom of the animal. Therefore, we hypothesize that SAX-7 functions in the CAN neurons to regulate fluid homeostasis. As a first step to testing this hypothesis, I examined the CANs in sax-7(0) Ras(gf) animals for morphological abnormalities that may underlie the fluid build-up in these animals. Here I present data that sax-7(0) Ras(gf) animals do indeed exhibit abnormal positioning of the CAN cell body and axon.
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Faculty advisor: Lihsia Chen
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This research was supported by the Undergraduate Research Opportunities Program (UROP).
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Qiu, David; Chen, Lihsia; Moseley-Alldredge, Melinda. (2021). Using C. elegans as a Model to Understand How sax-7 Effects Canal-Associated Neurons. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/219430.
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