Formation of tissue boundaries during zebrafish embryogenesis

Projektbeschreibung

Untersuchung der Entstehung von Gewebegrenzen im Zebrafischmodell

Fehler bei der Bildung von Gewebegrenzen werden häufig mit abnormalem Zellverhalten bei Krankheiten in Verbindung gebracht. Im Rahmen des EU-finanzierten Projekts DevBoundaries werden die Mechanismen der Entstehung von Gewebegrenzen in vivo untersucht, wobei der embryonale Schild des Zebrabärblings als Modellsystem dient. Der embryonale Schild ist eine evolutionär konservierte „Organisations“-Struktur, die für den Aufbau des gesamten Körperplans des Embryos entscheidend ist. Die über das Forschungsstipendium verfügende Person wird multidisziplinäre Ansätze anwenden, die Live-Bildgebung, räumliche Transkriptomik sowie genetische Manipulationen vereinen, um zu bestimmen, wie sich Schildzellen differenzieren und Gewebegrenzen bilden. Das Projekt wird zu einem umfassenden und dynamischen Atlas führen, der die Zellreihen, die Zellbewegungen sowie die Genexpression in der frühen Embryogenese von Wirbeltieren aufzeigt.

Ziel

During animal development, boundaries need to be reliably established between cell types to guarantee the physical and functional integrity of tissues. This process requires delicate orchestration of cell proliferation, differentiation and migration, and defects in tissue boundary formation are often linked with abnormal cell behaviours in diseases. Genetic programs involved in cell signalling and cell sorting across tissue boundaries have been previously identified, yet we still lack a systematic understanding of the mechanisms underlying boundary formation, because it has been challenging to analyse the coordination of gene expression, cell lineages and cell movement in space and time.

In this study, I will probe the in vivo mechanisms of tissue boundary formation using the zebrafish embryonic shield as a model system. The embryonic shield in zebrafish embryos is an evolutionarily conserved “organizer” structure that is critical for setting up the overall body plan of the embryos. The shield region contains overlapping progenitor cells that give rise to various tissue structures whose boundaries form and sharpen during gastrulation. However, the formation of shield progenitor cells into compartmentalized tissues has been a process that is poorly characterized, and the molecular and biophysical mechanisms that coordinate cell differentiation and morphogenesis to establish tissue boundaries remain elusive. I will utilize multi-disciplinary approaches that combine live imaging, spatial transcriptomics and genetic manipulation to determine how shield cells differentiate and generate tissue boundaries. I anticipate identifying cellular and genetic mechanisms controlling boundary formation, and provide a comprehensive and dynamic atlas detailing cell lineages, cell movement and gene expression of early embryogenesis in vertebrates.