Coordination of mouse embryogenesis in space and time at implantation

Introduction

Self-organisation is a defining feature of living systems and entails complex interplay between multiple parameters across various spatio-temporal scales. Using pre-implantation mouse embryos as a model system, our studies revealed a principle of regulative development, in which feedback between cell fate, polarity, and mechanics ensures robust control of embryo size, shape, and pattern.

Context of the Study

However, as embryos undergo implantation, this self-organisation mechanism has to be integrated into its spatio-temporal context. In this project, we aim to understand how developmental mechanisms are coordinated in space and time. The peri-implantation mouse embryo is an attractive system in which to study this coordination, as it begins to interact with uterine tissues, marks a key transition in morphogenesis, cell cycle, and growth, and exhibits a remarkable capacity for size regulation.

Methodology

We recently developed an ex vivo 3D culture, engineered uterus, and light-sheet microscopy to recapitulate morphogenesis and embryo-uterus interactions, and analyze changes in cell shape, fate, polarity, and mechanics. Using these new methods, we aim to mechanistically understand the transformation from blastocyst to egg cylinder as embryonic-extraembryonic tissues interact.

Research Objectives

We will use embryo size control as a paradigm to study the coordination of developmental programmes in space and time. Our specific objectives include:

1. Identifying what triggers the transition from cleavage to proliferative cell cycle – mammalian mid-blastula transition.
2. Understanding how animal size is sensed and how it changes the temporal progression of development.
3. Investigating the role of embryo-uterus interactions in embryo morphogenesis and positioning within the uterus.

Integration of Techniques

The bottom-up engineering approaches will be complemented by top-down intravital microscopy to monitor embryogenesis in utero. Together, this project will bring mammalian developmental biology into a new stage.