TIGP (BIO)—Decoding the principles of cell polarity through dynamic systems theory

Abstract

The diversity of cell morphology largely depends on the intracellular patterning of polarity proteins. For instance, Rho-GTPases pattern to only one polarity site in both the budding yeast and migrating mammalian cells. In contrast, the same Rho-GTPases can pattern to multiple polarity sites in both the branching hyphae of filamentous fungi and developing neurons. The mechanism by which different cells generate different numbers of polarity sites is profoundly important yet poorly understood.

Based on the budding yeast polarity machinery, we demonstrated that the patterning of polarity proteins can be understood through the theoretical framework of a mass-conserved reaction-diffusion (MCRD) system. In certain parameter regimes, polarity proteins patterning to a single site is the only stable steady state in MCRD systems. Correspondingly, we found that multiple initial polarity sites can form in the budding yeast, but they quickly compete with each other, resulting in only one single site. However, MCRD systems also predict that in other parameter regimes, such as higher protein content, multiple polarity sites can be stable or meta-stable, in which case they can stably exist simultaneously. We tested this prediction by genetically modifying the budding yeast. We confirmed that by increasing the amount of key polarity proteins, the budding yeast can overcome the natural tendency of competition between polarity sites and switch to growing multiple buds, resembling the growth mode of filamentous fungi. Furthermore, the MCRD framework also predicted that the same polarity machinery can lead to other polarity modes, which may correspond to the growth modes in not only the budding yeast but also other fungal species within Ascomycota. To test that, we use the fission yeast to understand how mono-polar growth can switch to bi-polar growth. These new insights gave rise to the possibility of utilizing Ascomycota as a model phylum to build a general theoretical framework for diverse cell polarity modes.
 
 
 

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