Aurora A depletion reveals centrosome-independent polarization mechanism in Caenorhabditis elegans

Author:

Klinkert Kerstin1ORCID,Levernier Nicolas23,Gross Peter4,Gentili Christian1,von Tobel Lukas1,Pierron Marie1,Busso Coralie1,Herrman Sarah1,Grill Stephan W456,Kruse Karsten237,Gönczy Pierre1ORCID

Affiliation:

1. Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), Lausanne, Switzerland

2. Department of Biochemistry, University of Geneva, Geneva, Switzerland

3. Department of Theoretical Physics, University of Geneva, Geneva, Switzerland

4. BIOTEC, TU Dresden, Dresden, Germany

5. Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

6. Cluster of Excellence Physics of Life, TU Dresden, Dresden, Germany

7. National Center of Competence in Research Chemical Biology, University of Geneva, Geneva, Switzerland

Abstract

How living systems break symmetry in an organized manner is a fundamental question in biology. In wild-type Caenorhabditis elegans zygotes, symmetry breaking during anterior-posterior axis specification is guided by centrosomes, resulting in anterior-directed cortical flows and a single posterior PAR-2 domain. We uncover that C. elegans zygotes depleted of the Aurora A kinase AIR-1 or lacking centrosomes entirely usually establish two posterior PAR-2 domains, one at each pole. We demonstrate that AIR-1 prevents symmetry breaking early in the cell cycle, whereas centrosomal AIR-1 instructs polarity initiation thereafter. Using triangular microfabricated chambers, we establish that bipolarity of air-1(RNAi) embryos occurs effectively in a cell-shape and curvature-dependent manner. Furthermore, we develop an integrated physical description of symmetry breaking, wherein local PAR-2-dependent weakening of the actin cortex, together with mutual inhibition of anterior and posterior PAR proteins, provides a mechanism for spontaneous symmetry breaking without centrosomes.

Funder

European Molecular Biology Organization

Fondation Bettencourt Schueller

H2020 European Research Council

Deutsche Forschungsgemeinschaft (DFG) under Germany ́s Excellence Strategy

Swiss National Science Foundation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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