Date of Award
Bachelor of Arts
Proper nervous system function depends upon myelin, a lipid-rich substance that facilitates rapid signal propagation by ensheathing neuronal axons. In different regions of the nervous system, specialized glial cells with distinct developmental lineages are responsible for producing myelin. In the central nervous system (CNS), neural stem cellderived oligodendrocytes (OLs) myelinate axons. Conversely, neurons of the peripheral nervous system (PNS) are myelinated by Schwann cells (SCs) derived from the neural crest. Both cell types have distinct genetic and molecular regulators throughout development, many of which have yet to be elucidated. To address this, a large-scale forward genetic screen in zebrafish was conducted to identify mutants with reduced expression of myelin basic protein (mbp), a marker for mature myelinating glia. From this screen, stl93 was isolated as a mutant with reduced mbp expression throughout the CNS. Interestingly, transmission electron microscopy (TEM) analyses revealed fewer total axons in the CNS, and fewer myelinated axons in the PNS of stl93 animals. To identify the causative mutation underlying these dual phenotypes in stl93, we analyzed whole-genome sequencing (WGS) and utilized genotyping assays to explore candidate genes. Furthermore, we used whole-mount in situ hybridization (WISH) to identify early glial development defects. Based on our current data, we hypothesize that a single locus regulating both neuron and glia development in the CNS and PNS is disrupted in stl93 animals.
Muppirala, Anoohya, "Exploring stl93: a novel Danio rerio neural development mutant with distinct axon and glial phenotypes in the CNS and PNS" (2019). Honors Theses. 232.
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