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Title: Genetic analysis of the Caenorhabditis elegans M1 neuron axon guidance and embryonic elongation
Author: Refai, Osama
Advisor: Paul, Mains
Keywords: Biology--Cell;Genetics;Biology--Molecular;Neuroscience
Issue Date: 18-Dec-2014
Abstract: Embryonic morphogenesis is a complicated process that involves several critical processes such as cell migration and body shape changes. The cell cytoskeleton is the basic machinery that drives many morphogenic events. Defects in regulators of the cytoskeleton components, especially actin and myosin, can result in birth defects. In this thesis, I carried out genetic analyses to study both morphogenesis of a single cell and the embryo as a whole in the nematode Caenorhabditis elegans. Axon guidance of the M1 neuron depends on multiple signaling cues and mechanisms. M1 uses the growth cone controlling genes such as unc-119, unc-51, unc-34 and unc-115 to build part of its trajectory. After its birth, M1 appears to use the mechanical tension to extend its initial projection, in a manner similar to another pharyngeal neuron M2. The g1P gland cell also participates in M1 guidance, analogous to glia cells or pioneer neurons. A forward genetic screen identified more genes that control M1 pathfinding including three novel genes. The variety of molecules and mechanisms used by the M1 neuron indicates that morphogenic processes at a single cell level are complicated and robust. Morphogenic processes are much more complicated in embryonic elongation, which involves the whole animal. Although major regulators of embryonic elongation have been identified, little is known about their function and genetic interactions. Here, I investigated the genetic interactions of the formin homology protein fhod-1 with other members of its family, showing that fhod-1 might be the sole formin acting in embryonic elongation. Additionally, I characterized the expression pattern of fhod-1, indicating it is expressed homogenously during elongation. Structural analysis of the fhod-1 gene identified a novel short isoform, which results from an alternative splicing event. Finally, I investigated the expression and function of the sex determination gene fem-2 in embryonic elongation. Although fem-2 is likely expressed ubiquitously in the epidermis, it appears to function specifically in dorsal/ventral epidermal cells to regulate elongation.
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