MOLECULAR MECHANISMS REGULATING CHROMOSOME SIZE SCALING DURING C. ELEGANS EARLY EMBRYONIC DEVELOPMENT Public Deposited

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  • March 20, 2019
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  • Ladouceur, Anne-Marie
    • Affiliation: College of Arts and Sciences, Department of Biology
Abstract
  • During embryonic development in metazoans, cells decrease in volume by up to two orders of magnitude, a consequence of multiple rounds of cell divisions without growth of the embryo. Using C. elegans and X. laevis embryo as model, it has been shown that mitotic structures all scale with cell size, smaller cells have smaller organelles (reviewed in [1]). Due to technical limitations, scaling of mitotic chromosome has received less attention. It is expected that during anaphase, condensed mitotic chromosomes must be half the length of the mitotic spindle to be properly segregated to each daughter cell, a length that varies according to cell size. Using high-resolution time-lapse microscopy of dividing C. elegans embryos, we have precisely measured chromosome length in 3D and show that prometaphase condensed chromosomes are smaller in length as cell reduces in size. We hypothesize that this change in chromosome condensation could be: 1) an outcome of a cellular size control and/or 2) a programmed developmental change. To assess the first hypothesis of a cell autonomous regulated mechanism, we experimentally reduced cell and nuclei size. Surprisingly, we found that reduction of each resulted in a corresponding reduction of chromosome size. To test the second hypothesis, we used a C. elegans strain with one chromosome longer than any wild-type chromosome, resulting from a X/autosomeV end-to-end chromosome fusion. This worm strain should be sensitive to any defect in chromosome condensation or segregation. To identify new regulators of chromatin compaction, we depleted known chromatin modifying enzymes and identify genes that increased embryonic lethality in the fusion strain compared to a WT strain. This strategy allowed us to identify both CENP-A and Topoisomerase II as crucial chromosome size regulators during C. elegans early embryonic development. Thus we are using large-scale RNAi depletion and high resolution imaging to determine the mechanisms of mitotic chromosome size regulation. Mitotic chromosome assembly and the process of scaling organelles to cell size are often seen as cellular processes. Indeed, this project highlights an innovative idea since those problems are poorly understood in a developmental context.
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  • In Copyright
Advisor
  • Ahmed, Shawn
  • Bautch, Victoria
  • Duronio, Robert
  • Maddox, Paul
  • Bloom, Kerry
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
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