How do cells form an embryo: Intracellular, temporal, and phenotypic dissection of mammalian gastrulation

Introduction

In multicellular organisms, how variation is achieved while cells comprise identical genetic information represents a fundamental open challenge my group strives to engage in the coming years. The development of a single fertilized egg into a complete embryo represents an especially beautiful embodiment of this problem.

Differentiation Process

The process of differentiation is defined by the capacity of the cell ensemble to acquire increasingly more specialized internal states in a coordinated fashion. We are therefore excited by recent breakthroughs in single-cell transcriptomics and epigenomics since these can capture the emergence of embryonic cellular diversification at incredible resolution.

Need for Integration

However, we believe there is an urgent need in the field to match descriptive single-cell atlases with models and experimental frameworks to derive novel understanding of function and regulation in this process.

Research Approaches

To this end, we will undertake three complementary approaches – all implemented during specification of the basic mammalian body plan (gastrulation) in vivo:

1. Scrutinizing Differentiation
   We will scrutinize parallel and converged differentiation in embryonic and extraembryonic lineages at absolute time. This will be achieved in both mouse and rabbit, providing unprecedented molecular insight into the evolutionary hourglass theory.

2. Dissecting Epigenetic Mechanisms
   Building on our recently developed capabilities, we will systematically dissect epigenetic mechanisms shaping and memorizing intracellular states. Importantly, we will do so by controlling for cell type and effects that propagate in and between tissues over time.

3. Charting Extracellular Signaling
   Finally, we will chart and manipulate extracellular signaling affecting cell specification in the 3D embryonic space.

Expected Outcomes

Our study will provide mechanistic understanding and much-needed quantitative models that truly represent embryonic development as a concurrent interacting ensemble with far-reaching implications for other fields, such as regenerative medicine, cancer, aging, and synthetic embryogenesis.