Formation of tissue boundaries during zebrafish embryogenesis

Descripción del proyecto

Cómo se generan las separaciones entre tejidos en modelos de pez cebra

Cuando en las separaciones entre tejidos aparecen fallos, estos suelen guardar relación con comportamientos celulares anómalos en las enfermedades. El proyecto financiado con fondos europeos DevBoundaries investigará «in vivo» los mecanismos que rigen la formación de separaciones entre tejidos y usará el disco germinativo del pez cebra como sistema modelo. El disco germinativo es una estructura «organizadora» conservada a lo largo de la evolución que resulta fundamental en la organización de la planificación general del cuerpo embrionario. El investigador al cargo empleará métodos multidisciplinarios que combinan obtención de imágenes en vivo, transcriptómica espacial y manipulación genética para determinar el modo en el que las células del disco se diferencian y generan separaciones entre tejidos. El proyecto generará un atlas exhaustivo y dinámico en el que se muestren linajes celulares y expresiones génicas de las primeras fases de la embriogénesis en vertebrados.

Objetivo

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.