Talk abstracts

Talk on Tuesday 03:15-03:30pm submitted by Shayne Plourde

Asymmetric Centrosome Maturation in the Early C. elegans Embryo: Insights from Multi-scale Microscopy and Modeling

Shayne M. Plourde (MCDB), Natalia Kravtsova (Mathematics), Adriana T. Dawes (Molecular Genetics & Mathematics)

Abstract:
How the two centriole pairs, and their corresponding centrosomes, of a cell are positioned is critically important to stem cells and perturbations in this process can be observed in many diseases and cancer development. In C. elegans the positioning of centrosomes during development is critical for the asymmetric divisions used to determine the germline lineage of cells. Previous work has shown an asymmetry in the microtubule arrays nucleated by the two centrosomes that set up these divisions; however, the functional origin of this asymmetry is unknown. We precisely quantified the fluorescence recruitment and recovery of a centrosomal Aurora A kinase, AIR-1 in C. elegans, that is required for proper MT nucleation. We show that the maturation of the two centrosomes in the 1 cell embryo are not symmetric but their recoveries after photobleach are similar. Using this data to parameterize a novel mathematical model identified a difference in the cooperativity of the centrosomes that could explain the difference in slow recruitment dynamics but not in the fast recovery dynamics. Further, we tracked the inheritance of the oldest centrioles into the 4 cell stage and observed a potential age related inheritance pattern. The multi-scale microscopy and mathematical modeling together tell us that there is a potential asymmetry inside of the centrosome that is directly connected to cell fate decisions and potentially to disease progression.

References:
Valerie C. Coffman et al. Stronger net posterior cortical forces and asymmetric microtubule arrays produce simultaneous centration and rotation of the pronuclear complex in the early Caenorhabditis elegans embryo. Mol. Biol. Cell, 27(22):3550–3562, nov 2016

Alexander Woglar et al. Molecular architecture of the C. elegans centriole. PLoS Biol., 20(9):e3001784, sep 2022

Adriana Dawes et al. Efficient identification of parameter space structure with Modified Metropolis-Hastings algorithm, 14 March 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-2579700/v1]

Keywords: Asymmetry, Computational, Centrosome