Planar Differential Growth Rates Initiate Precise Fold Positions in Complex Epithelia.

Melda Tozluoǧlu,Maria Duda,Jemima J Burden,Ricardo Barrientos,Natalie J Kirkland,José J Muñoz,Yanlan Mao

doi:10.1016/j.devcel.2019.09.009

Abstract

SummaryTissue folding is a fundamental process that shapes epithelia into complex 3D organs. The initial positioning of folds is the foundation for the emergence of correct tissue morphology. Mechanisms forming individual folds have been studied, but the precise positioning of folds in complex, multi-folded epithelia is less well-understood. We present a computational model of morphogenesis, encompassing local differential growth and tissue mechanics, to investigate tissue fold positioning. We use the Drosophila wing disc as our model system and show that there is spatial-temporal heterogeneity in its planar growth rates. This differential growth, especially at the early stages of development, is the main driver for fold positioning. Increased apical layer stiffness and confinement by the basement membrane drive fold formation but influence positioning to a lesser degree. The model successfully predicts the in vivo morphology of overgrowth clones and wingless mutants via perturbations solely on planar differential growth in silico.

Highlights

Epithelial folding is a fundamental morphological process that is encountered abundantly during the development of multiple organisms
From experimental measurements, we demonstrate that the differential growth in the plane of the tissue, especially in the early stages, under the compression of the extracellular matrix (ECM), drives the initiation of three folds from the apical surface
The Computational Model For the purposes of identifying the mechanisms driving wing disc folding, we develop a finite element (FE) model (Bonet and Wood, 2008) of tissue morphogenesis

Summary

Introduction

Epithelial folding is a fundamental morphological process that is encountered abundantly during the development of multiple organisms. Other force generation mechanisms, such as cell rounding in mitosis, adhesion shifts, or basal extrusions can induce folds (Kondo and Hayashi, 2013, 2015; Monier et al, 2015; Wang et al, 2012). In all these scenarios, what defines the position of the prospective fold is a biochemical signaling mechanism responsible for selecting the cell population to actively generate the forces

Methods

Results

Discussion

Conclusion