Coupling morphogen dynamics with mechanics in the control of form and pattern

Introduction

Embryogenesis entails both the generation of cell type diversity and large-scale morphogenetic movements sculpting the forming body axes. How patterning and morphogenesis are each individually controlled is increasingly understood, yet how these fundamental processes are coordinated remains an open question in biology.

Background

My recent work in zebrafish gastrulation, a crucial developmental stage where the germ layers are specified and shaped, provided a conceptual framework for how patterning and morphogenesis can be coupled by morphogen signalling. However, how a small set of highly conserved morphogens mechanistically controls a striking diversity of biological functions across many developmental systems remains unclear.

Research Gap

This is especially true as little is known about how morphogen signalling encodes the mechanical forces organizing morphogenesis. We hypothesize that examining the multiscale interplay between morphogen dynamics and mechanics will provide the missing link to understand how the emergence of pattern and form are coordinated by a handful of morphogens.

Objectives

Using both zebrafish embryos and human 2D gastruloids, we aim to uncover:

1. How the dynamics of morphogen signalling encodes the mechanical properties organizing morphogenesis.
2. How cell and tissue mechanics, in turn, modulate morphogen signalling dynamics and robust patterning.
3. How cells decode dynamical mechanochemical inputs to instruct cell fate and patterning.

Methodology

Towards these goals, we will combine our expertise in biophysics and developmental biology with recent advances in live-cell signalling reporters, optogenetics, biophysical tools, and gastruloid models to quantitatively understand the design principles and molecular effectors of the cross-talk between morphogen dynamics and mechanics.

Implications

This will generate novel insights relevant beyond developmental biology, with direct implications for the engineering of organoid technologies, regenerative medicine, and our understanding of the evolution of form and pattern.