MassIVE MSV000095250

Complete Public PXD053646

Molecular Basis of Spindle Morphology Changes at the Meiosis to Mitosis Transition

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Description

The transition from meiotic divisions in the oocyte to mitotic divisions in the early embryo is a critical step in animal development. Despite negligible changes to cell size, shape, and content, following fertilization the small, barrel-shaped meiotic spindle is replaced by a large zygotic spindle that nucleates abundant astral microtubules at spindle poles. To identify underlying mechanisms, we applied a drug screening approach using eggs of the simple chordate Ciona robusta (sea squirt) and found that inhibition of Casein Kinase 2 (CK2) caused a shift from meiotic to mitotic-like spindle morphology with nucleation of robust astral microtubule arrays, an effect reproduced in Xenopus laevis (frog) egg extracts. In both species, a kinase assay revealed that CK2 activity decreases at fertilization. To identify substrates and downstream effectors, we assessed the global phosphoproteomic changes that accompany both the meiosis to mitosis transition and CK2 inhibition in Xenopus, which identified components of the Ran-GTP pathway as potential downstream targets. Inhibition of Ran-GTP-driven microtubule nucleation suppressed CK2-induced spindle morphology changes in both Xenopus and Ciona. These data support a model in which attenuation of CK2 activity at fertilization in chordates leads to activation of Ran-regulated spindle assembly factors that drive microtubule growth and the transition to mitotic spindle morphology. [doi:10.25345/C5WW77B31] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Frog, mitosis, meiosis, embryo, cell cycle phases

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Principal Investigators:
(in alphabetical order) 		Arminja Nadine Kettenbach, Dartmouth College, United States
Submitting User: Arminja
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