Emergence of planar cell polarity from the interplay of local interactions and global gradients

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Abstract

Planar cell polarity (PCP) – tissue-scale alignment of the direction of asymmetric localization of proteins at the cell-cell interface – is essential for embryonic development and physiological functions. Abnormalities in PCP can result in developmental imperfections, including neural tube closure defects and misaligned hair follicles. Decoding the mechanisms responsible for PCP establishment and maintenance remains a fundamental open question. While the roles of various molecules – broadly classified into “global” and “local” modules – have been well-studied, their necessity and sufficiency in explaining PCP and connecting their perturbations to experimentally observed patterns have not been examined. Here, we develop a minimal model that captures the proposed features of PCP establishment – a global tissue-level gradient and local asymmetric distribution of protein complexes. The proposed model suggests that while polarity can emerge without a gradient, the gradient not only acts as a global cue but also increases the robustness of PCP against stochastic perturbations. We also recapitulated and quantified the experimentally observed features of swirling patterns and domineering non-autonomy, using only three free model parameters - the rate of protein binding to membrane, the concentration of PCP proteins, and the gradient steepness. We explain how self-stabilizing asymmetric protein localizations in the presence of tissue-level gradient can lead to robust PCP patterns and reveal minimal design principles for a polarized system.

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The current manuscript is a computational study, so no data have bene generated for this manuscript. Modeling code used is available on GitHub page of D.S. (https://github.com/Divyoj-Singh/Planar cell polarity).

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Divyoj Singh

Centre for BioSystems Science and Engineering, Indian Institute of Science Bangalore, Bengaluru, India

Competing interests
The authors declare that no competing interests exist.
Sriram Ramaswamy

Department of Physics, Indian Institute of Science Bangalore, Bengaluru, India

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-7726-8556
Mohit Kumar Jolly

Centre for BioSystems Science and Engineering, Indian Institute of Science Bangalore, Bengaluru, India

For correspondence
mkjolly@iisc.ac.in

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6631-2109
Mohd Suhail Rizvi

Department of Biomedical Engineering, Indian Institute of Technology Hyderabad, Hyderabad, India

For correspondence
suhailr@bme.iith.ac.in

Competing interests
The authors declare that no competing interests exist.

Funding

Science and Engineering Research Board (SB/S2/RJN-049/2018)

Mohit Kumar Jolly

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.