A semi-dominant mutation in the general splicing factor SF3a66 causes anterior-posterior axis reversal in one-cell stage C. elegans embryos.

Mohammad R Keikhaee,Bruce Bowerman,Sean M O'Rourke,Eric B Nash,Henry H Roehl

doi:10.1371/journal.pone.0106484

Mohammad R Keikhaee, Bruce Bowerman + Show 3 more

Open Access

https://doi.org/10.1371/journal.pone.0106484

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Journal: PloS one	Publication Date: Sep 4, 2014
Citations: 3	License type: CC BY 4.0

Affiliation: University of Oregon

Abstract

Establishment of anterior-posterior polarity in one-cell stage Caenorhabditis elegans embryos depends in part on astral microtubules. As the zygote enters mitosis, these microtubules promote the establishment of a posterior pole by binding to and protecting a cytoplasmic pool of the posterior polarity protein PAR-2 from phosphorylation by the cortically localized anterior polarity protein PKC-3. Prior to activation of the sperm aster, the oocyte Meiosis I and II spindles assemble and function, usually at the future anterior pole, but these meiotic spindle microtubules fail to establish posterior polarity through PAR-2. Here we show that a semi-dominant mutation in the general splicing factor SF3a66 can lead to a reversed axis of AP polarity that depends on PAR-2 and possibly on close proximity of oocyte meiotic spindles with the cell cortex. One possible explanation is that reduced levels of PKC-3, due to a general splicing defect, can result in axis reversal due to a failure to prevent oocyte meiotic spindle microtubules from interfering with AP axis formation.

Highlights

Asymmetric cell division is a fundamental process that generates cell fate diversity [1,2]
The initially cytoplasmic posterior polarity protein PAR-2 localizes to the cortical region vacated by PAR-3, and subsequent mutually antagonistic interactions between PAR-2 and PAR-3 lead to the expansion of a posterior cortical PAR-2 domain and the eventual establishment of a fully polarized zygote [12]
Based on our analysis of PKC-3 and oocyte meiotic spindles, it is possible that reduced levels of cortical PKC-3 activity or expression in repo-1(or430ts) mutants allow PAR-2 to better associate with the anterior cortex and reverse the AP axis of polarity, due to oocyte meiotic spindle microtubules protecting PAR-2 from PKC-3 phosphorylation, much as other microtubules normally appear to promote formation of a posteriorly positioned cortical PAR-2 domain

Summary

Introduction

Asymmetric cell division is a fundamental process that generates cell fate diversity [1,2]. The sperm-donated centrosome may provide additional cues, the astral microtubules it nucleates, or other microtubules, appear to play a critical role in specifying the posterior pole [6,7] They do so at least in part by binding to PAR2 and protecting it from phosphorylation by PKC-3, the atypical protein kinase C that associates with PAR-3 as part of the anterior cortical PAR complex [13]. The oocyte Meiosis I and II spindles function prior to sperm aster activation and usually are positioned at the future anterior pole [14] These microtubules could bind to and protect PAR-2 from PKC-3 phosphorylation. It is possible that one role for PKC-3 is to prevent oocyte meiotic spindles from interfering with AP axis formation, and that reduced expression of PKC-3 due to a general splicing defect can lead to axis reversal

Results

Discussion

Materials and Methods