Date of Award

May 2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Advisor(s)

Heidi Hehnly

Subject Categories

Life Sciences

Abstract

During embryonic tissue morphogenesis, cell division increases both the number of cells and cellular diversity. This is often regulated by the positioning of daughter cells post-mitosis. The goal of this dissertation research is to determine the mechanisms that place daughter cells, and how this contributes to tissue development. First, the zebrafish left-right organizer, Kupffer’s vesicle (KV) is used as a model to investigate the role of cytokinesis and abscission during de novo lumen formation. The cytokinetic bridge places at the center of the developing KV rosette, where it acts as a landmark for Rab11-mediated vesicle trafficking to bring polarity components such as CFTR to the site of future lumen formation. Next, the early zebrafish embryo is used as a model to determine how the spindle is oriented to create a monolayer grid formation prior to three-dimensional embryo expansion. Here, the mitotic spindles are oriented parallel to each other and perpendicular to the previous cell division plane. A stark asymmetry in spindle pole size creates a directionality in this spindle positioning, where the larger spindle pole points towards the center of the embryo in a PLK1- and PLK4-dependent manner. Lastly, a local drug delivery system was developed in zebrafish embryos to target a PLK1 inhibitor to the centrosome. Through this system, it was revealed that centrosomal PLK1 is responsible for spindle organization and mitotic progression in zebrafish embryos. Taken together, this work describes how the contribution of cell division to tissue morphogenesis is tissue-specific, raising the argument that further cell division studies should be conducted in vertebrate systems to understand mitosis in a three-dimensional tissue context.

Access

Open Access

Available for download on Saturday, July 02, 2022

Included in

Life Sciences Commons

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