Investigating the mechanisms of endoderm and mesoderm segregation

This is a summer student position supervised by Natalia Jaroszynska in Caroline Hill's lab.

Introduction to the science

The Developmental Signalling lab is interested in understanding how cells communicate with their environment and with each other using extracellular signals that induce new programmes of gene expression and regulate cell behaviours. This is studied in the fundamental context of embryonic development and human disease.

About the project

A central question in developmental biology is understanding how initially identical cells are specified to become distinct organs and simultaneously organise themselves precisely along the body axis to give rise to an embryo. In the zebrafish embryo, the same stem cells give rise to both the cells of the gastrointestinal (endoderm) and cardiovascular, muscle and bone (mesoderm) systems, despite being exposed to the same signals. How these two initially identical and intermixed cell populations segregate from one another transcriptionally as well as physically to form distinct lineages and tissue types, while undergoing anterior-posterior patterning and global cellular movements, remains unclear. Using single cell RNA-seq analyses, we have identified several novel genes unique to endodermal cells that may be involved in their lineage commitment, migration, adhesion and signalling. These processes in turn are likely involved in instructing the separation of endodermal and mesodermal progenitors into distinct populations, and eventually into the correct organs in the right place and at the right time. In this project, the aim is to explore the role of some of these candidate genes in endodermal migration and lineage commitment in live and fixed zebrafish embryos by using a range of techniques, such as CRISPR/Cas9 mutagenesis, single molecule fluorescence in situ hybridisation (FISH) and confocal microscopy to visualise gene expression. This will further our understanding of fundamental mechanisms that orchestrate the building of organ systems and ultimately functional embryos.

Candidate background