General Mechanisms of Morphogenesis on Multiple Scales

This project aims to advance the understanding of Morphogenesis - the process of biological “shape formation” – which is central to animal and plant development and is a fundamental open problem in the study of Living Matter. Recent discoveries in this interdisciplinary field have established the importance of mechanical interactions that guide growing tissues into diverse shapes and forms of adult organisms.

The present project will address the problem on multiple scales, from subcellular to organismal, focusing on several laboratory model systems of animal and plant development. Planned work aims to understand intracellular processes underlying generation of mechanical tension in tissues, and will investigate the role of mechanical interactions during embryonic development.

The project will also provide a general mathematical description of how patterns of tissue growth define the shapes of animal limbs and plant leaves. Progress in understanding morphogenetic processes across developmental systems is fundamental to the advancement in health and agriculture.

The project will focus on the interplay between active mechanical self-organization of tissues and the genetically encoded developmental signals that guide morphogenesis. On the subcellular scale, it will seek to identify the dynamical mechanisms underlying the adaptive response of cells to mechanical stress and the rate of strain. On the scale of tissues, the project will investigate the role of mechanical feedback-driven self-organization in morphogenetic tissue rearrangement in the fruit fly embryo.

Lastly, on the organismal level, the project will investigate alternative spatio-temporal strategies of two-dimensional (2D) tissue growth that define three-dimensional (3D) shapes in both plants and animals. Specifically, the project will:

1. Develop a mechanical self-organization model of epithelial tissue flow during gastrulation of the Drosophila embryo and validate it by comparing with the quantitative data from collaborating labs. This study is motivated by the recently uncovered failure of the widely accepted gene expression-based model to quantitatively explain such morphogenetic flow.

If successful, this project will change the conceptual framework underlying a key aspect of embryonic morphogenesis of the fruit fly, an important model system in the study of animal development.

2. Develop a model of junctional cytoskeleton self-assembly - an example of intracellular morphogenesis - to elucidate the sub-cellular mechanism of feedback that, by sensing the rate of strain, stabilizes mechanical self-organization on the tissue scale. This model will also define experimental diagnostics for the otherwise inaccessible dynamic state of the cytoskeleton.

3. Develop a general representation of 3D shape formation by anisotropic growth of 2D epithelial sheets, and characterize the space of alternative morphogenetic growth strategies leading to the same final shape. This project will frame the problem of the selection of growth strategies as a general variational principle, and test the ideas by comparing predictions with quantitative observations of morphogenetic growth trajectories in different biological systems, specifically: the growth of flower primordia, and the growth of a crustacean limb.

To broaden its impact the project will leverage the convening infrastructure of the KITP Interdisciplinary Biology Initiative led by the PI to organize an online “Tutorial Forum” connecting biophysics and developmental biology with the goal of attracting young scientists to this field and increasing its demographic diversity. The PI will also organize a one-day online Teachers' Conference for high-school science teachers across the US, aiming to bring to them the intellectual excitement of interdisciplinary science.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.