Modeling the establishment of PAR protein polarity in the one-cell C. elegans embryo
Filipe Tostevin1, Martin Howard
1Department of Mathematics, Imperial College London, London, United Kingdom.
Insights
This study models C. elegans embryo polarity establishment, revealing that known PAR protein interactions explain cortical dynamics. Cytoplasmic asymmetry is also critical for proper PAR protein localization in daughter cells.
Area of Science:
- Cellular Biology
- Developmental Biology
- Biophysics
Background:
- C. elegans embryo polarity is established along the anterior-posterior axis at the one-cell stage.
- PAR proteins (PAR-3/PAR-6/PKC-3 and PAR-1/PAR-2) form distinct cortical domains driven by cytoskeletal rearrangement after fertilization.
- Cortical actomyosin contraction is a key event initiating anterior-posterior polarity.
Purpose of the Study:
- To develop a mathematical model combining PAR protein reaction-diffusion dynamics with actomyosin contraction.
- To investigate the sufficiency of known PAR protein interactions in explaining observed cortical polarity.
- To explore additional mechanisms required for proper cytoplasmic PAR protein polarity.
Main Methods:
- Mathematical modeling integrating reaction-diffusion dynamics of PAR proteins.
- Coupling PAR protein dynamics with a model of cortical actomyosin contraction.
- Analysis of both wild-type and mutant C. elegans embryos.
Main Results:
- The model successfully explains many aspects of cortical PAR protein dynamics using known interactions.
- Existing models are insufficient to explain cytoplasmic PAR protein polarity.
- The model predicts that cytoplasmic cytoskeletal asymmetry is crucial for PAR protein localization.
Conclusions:
- Known PAR protein interactions are sufficient to explain cortical polarity establishment in C. elegans embryos.
- Cytoplasmic PAR protein polarity requires mechanisms beyond cortical dynamics, specifically cytoskeletal asymmetry.
- Cytoplasmic and cortical asymmetries together critically determine PAR protein localization during early development.
Abstract:
At the one-cell stage, the C. elegans embryo becomes polarized along the anterior-posterior axis. The PAR proteins form complementary anterior and posterior domains in a dynamic process driven by cytoskeletal rearrangement. Initially, the PAR proteins are uniformly distributed throughout the embryo. After a cue from fertilization, cortical actomyosin contracts toward the anterior pole. PAR-3/PAR-6/PKC-3 (the anterior PAR proteins) become restricted to the anterior cortex. PAR-1 and PAR-2 (the posterior PAR proteins) become enriched in the posterior cortical region. We present a mathematical model of this polarity establishment process, in which we take a novel approach to combine reaction-diffusion dynamics of the PAR proteins coupled to a simple model of actomyosin contraction. We show that known interactions between the PAR proteins are sufficient to explain many aspects of the observed cortical PAR dynamics in both wild-type and mutant embryos. However, cytoplasmic PAR protein polarity, which is vital for generating daughter cells with distinct molecular components, cannot be properly explained within such a framework. We therefore consider additional mechanisms that can reproduce the proper cytoplasmic polarity. In particular we predict that cytoskeletal asymmetry in the cytoplasm, in addition to the cortical actomyosin asymmetry, is a critical determinant of PAR protein localization.
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