Cell segregation in gastrulation: the role of cell fate specification

In this interdisciplinary research proposal, we will determine the relationship between progenitor cell fate specification the reversible process by which blastoderm cells become capable of differentiating into ectoderm, mesoderm and endoderm cells and progenitor cell-cell contact formation in driving germ layer formation during zebrafish gastrulation. We will determine how progenitor cell fate specification and cell-cell contact formation influence each other during gastrulation, and how their interaction influences progenitor cell segregation and tissue organization. Specifically, we will address the following questions: i) How are progenitor cell-cell contact formation, cell fate specification and cell segregation correlated in space and time? ii) How do progenitor cell-cell contact formation, cell fate specification and cell segregation influence each other? iii) What molecular and cellular mechanisms control the interplay between progenitor cell-cell contact formation, cell fate specification and cell segregation? We expect that addressing these fundamental questions will provide novel insight into the interplay between progenitor cell-cell contact formation and cell fate specification, and the role this interplay has in controlling progenitor cell segregation during gastrulation.

Cell-cell contact formation constitutes the first step in the emergence of multicellularity in evolution, thereby allowing the differentiation of specialized cell types. In metazoan development, cell-cell contact formation is thought to influence cell fate specification, and cell fate specification has been implicated in cell-cell contact formation. In this project, we identify a positive feedback loop between cell-cell contact duration, morphogen signaling and mesendoderm cell fate specification during zebrafish gastrulation. We show that long lasting cell-cell contacts enhance the competence of prechordal plate (ppl) progenitor cells to respond to Nodal signaling, required for proper ppl cell fate specification. We further show that Nodal signalling promotes ppl cell-cell contact duration, thereby generating an effective positive feedback loop between ppl cell-cell contact duration and cell fate specification. Our findings reveal that the gene regulatory networks leading to cell fate diversification within the developing embryo are controlled by the interdependent activities of cell-cell signaling and contact formation.