Actomyosin Spatiotemporally Regulates Par Polarity Dynamics To Create Neural Stem Cell Asymmetry
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Date
2021-09-13
Authors
Oon, Chet Huan
Journal Title
Journal ISSN
Volume Title
Publisher
University of Oregon
Abstract
Pattern formation, or specifically symmetry breaking, is a fundamental process essential for proper asymmetric cell division. In asymmetrically dividing stem cells, the evolutionarily conserved Par polarity complex localizes to a discrete Par domain to facilitate unequal distribution of fate determinants into the daughter cells–thereby ensuring a binary cell division outcome where daughters will acquire distinct fates. Hence proper asymmetric cell division requires the spatiotemporal distribution of Par proteins to be precisely coordinated. While a number of studies have been conducted to understand how Par activity creates downstream asymmetry, how the Par complex acquires asymmetry remains unclear. Two standing models exist to explain for how Par proteins can become polarized. In the one-cell stage C. elegans embryo, gradients of contractile force created by the cortical actomyosin cytoskeletal network generates cortical flow towards the anterior pole. Concurrently, symmetrical Par proteins that are entrained within the network becomes advected via bulk motion of the cortex, consequently becoming anteriorly segregated. In Drosophila neuroblasts, Par complex exchanges between the unpolarized, cytoplasmic and polarized, apical states; it is thus thought to become polarized to the apical domain via a direct, asymmetric targeting mechanism.
In this dissertation, we examined the spatiotemporal distribution profile of cortical Par proteins and actomyosin in mitotic neuroblasts using a full volume, rapid live imaging approach to capture change in cortical protein distribution as they transition from an unpolarized to a polarized state. In the second chapter, we characterized the Par protein dynamics and investigated if the actomyosin network is essential for Par dynamics. This study demonstrated that Par polarization is a dynamic, multistep process, consisting of asymmetric targeting of cytoplasmic Par into discrete, apical foci and F-actin dependent coalescence of Par foci at the apical pole. In the third chapter, we determined the cortical dynamics of actomyosin and identified that coalescence is spatiotemporally linked to myosin II driven flow. Our studies suggest a conserved role for actomyosin in Par polarity in C. elegans embryos and Drosophila neuroblasts.
This dissertation contains previously published and unpublished co-authored material. Live imaging movies of Par proteins and actomyosin are attached in the supplemental files associated with this dissertation.
Description
PDF of dissertation and zipped file of 13 videos.
Keywords
actomyosin, asymmetry, cell polarity, neuroblast