A theoretical framework for planar polarity establishment through interpretation of graded cues by molecular bridges.

Katherine H Fisher,David Strutt

doi:10.1242/dev.168955

Abstract

ABSTRACTPlanar polarity is a widespread phenomenon found in many tissues, allowing cells to coordinate morphogenetic movements and function. A common feature of animal planar polarity systems is the formation of molecular bridges between cells, which become polarised along a tissue axis. We propose that these bridges provide a general mechanism by which cells interpret different forms of tissue gradients to coordinate directional information. We illustrate this using a generalised and consistent modelling framework, providing a conceptual basis for understanding how different mechanisms of gradient function can generate planar polarity. We make testable predictions of how different gradient mechanisms can influence polarity direction.

Highlights

Many animal tissues show coordinated polarisation of cells along a planar axis
In this Hypothesis, we present a theoretical framework to explore the theory that molecular bridges between cells provide a general mechanism by which gradients are interpreted to achieve planar polarisation in animal tissues
It further follows that the observed distal to proximal Wg/Wnt4 gradient in the wing could act as an effective planar polarity cue for the core pathway if two conditions hold: (1) the default state of Fz is ‘active’ (i.e. Fz*, able to bind Fmi) and Wg/Wnt4 binds to Fz* and converts it to Fz; and (2) this binding/modification is stable and retained as Fz redistributes within cells

Summary

Introduction

Many animal tissues show coordinated polarisation of cells along a planar axis. Such planar polarisation results in the coordinated placement and function of external structures, such as hairs or cilia (Fig. 1A,B), or in coordination of morphogenetic movements (reviewed by Butler and Wallingford, 2017; Davey and Moens, 2017). Produced from localised sources, they form concentration gradients as they spread throughout surrounding tissue Such graded signals can specify cell fate, regulate tissue size and provide directional cues to specify planar polarity (reviewed by Strutt, 2009; Rogers and Schier, 2011; Inomata, 2017). At the top of the gradient, this difference needs to be read against the background of a high overall expression level, while at the low end of the gradient, noise may lead to mispolarisation of individual cells In this Hypothesis, we present a theoretical framework to explore the theory that molecular bridges between cells provide a general mechanism by which gradients are interpreted to achieve planar polarisation in animal tissues (see Struhl et al, 2012; Lawrence and Casal, 2018). Fjdependent phosphorylation of the atypical cadherins Ft and Ds can determine their planar polarised localisation to opposite cell ends, A

C Intercellular gradient D Intracellular gradient

A B Cell i-1

A Complex C3

B Complex C3

Findings

A Local conversion of A to A*