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Advisory Committee Chair

Chenbei Chang

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

During embryonic development of all animal species, dramatic changes in morphology occur to transform a single-celled zygote into a well-organized adult body that contains different organs positioned in stereotypical ways for the species. The processes that shape tissues and organs are called morphogenesis, and gastrulation is the first morphogenetic process in embryogenesis. During gastrulation, three germ layers are specified and a set of regionally specific cell movements act in concert to position these germ layers for proper establishment of future body plan of the developing animal. Although factors regulating cell lineage specification have been studied extensively, the molecular machinery controlling region-specific behaviors is less understood. In this study, we performed RNA-sequencing experiments to identify genes differentially expressed among various tissues during gastrulation, using the animal Xenopus laevis as our model. Xenopus gastrulation, as in other species, utilizes distinct cell behaviors, including cell shape changes (e.g. apical constriction), cell migration, and cell intercalation in different embryonic regions. These cell behaviors are preserved when tissues are isolated from the whole embryos. We sought to identify genes that are associated with different regions at developmental time points when cells in these regions exhibit characteristic behaviors. We aim to link these differentially expressed genes to cell behaviors they may be responsible for promoting. Identification of regulators of cell behaviors during gastrulation can help to provide paradigms for understanding analogous cell behavior regulation seen in other contexts, both during embryogenesis and in adult. Our results highlight several regionally enriched genes potentially involved in modulation of cell adhesion, extracellular matrix assembly, and modification of the cytoskeleton, the roles for many of these genes in development are previously unknown. Particularly, we investigate a secreted protein kinase, pkdcc1, and show that it is an important component in pathways regulating both migration of anterior mesendoderm and convergent extension of the prospective trunk. In addition, we describe an essential role for the Rho guanine nucleotide exchange factor plekhg5 in induction of apical constriction within the bottle cells, which define the site of involution cell movements during gastrulation. Our studies thus uncover crucial function of previously uncharacterized regulators of cell movements.

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