Regulation of mesoderm fate patterning through multiscale dynamics - PROJECT SUMMARY Human development intricately relies on precise fate determination during gastrulation, a pivotal stage where a uniform epithelium undergoes dynamic rearrangement to form the diverse tissues of the body plan. Classical embryology has identified pathways and gene expression patterns guiding predictable tissue formation, yet emerging hypotheses reveal a deeper complexity in cellular behavior and fate determination. When a cell dynamically alters its physiology to migrate in response to nearby signals, its microenvironment undergoes continuous changes as it moves. How does the cell interpret these dynamic shifts to regulate its downstream functions effectively? This proposal delves into the dynamics of early mammalian development, focusing on mesoderm cell behavior during gastrulation and its implications for tissue formation and cell fate. I aim to challenge the conventional notion of embryonic development as a linear series of phases by dissecting the interplay between cell movement and the changing milieu, highlighting the dynamic and non-linear nature of tissue formation. Exploiting an in vitro gastruloid model, I will explain the mechanisms underlying mesoderm migration, offering a unique opportunity to dissect migration dynamics and their impact on tissue organization. My preliminary data suggests that mesoderm cells exhibit high motility and contribute significantly to downstream tissue organization, highlighting the potential of altering migration kinetics to influence mesoderm architecture. Through a combination of genetic perturbations, functional analysis, and computer vision, this proposal aims to establish a novel approach to understand the regulatory pathways governing mesoderm migration and its role in tissue architecture. How does the physical environment dynamically influence mesoderm fate? To address this question, my project is twofold: firstly, unraveling the mechanisms regulating mesoderm cell migration during fate patterning; and secondly, understanding how migration dynamics shape tissue form and influences cell fate decisions. Overall, this study aims to uncover fundamental insights into the complexity of mesoderm cell behavior during embryonic development. These findings contribute to our broader goal of understanding and eventually controlling cell behavior.
