Separation of different cell types by tissue boundaries is a hallmark of all multi-cellular organisms. During animal development, boundaries between tissues not only arise to achieve physical and functional segregation between neighbouring groups of embryonic cells, but also serve as signalling centres that control downstream patterning events . Changes in the location or integrity of tissue boundaries often lead to severe defects in development, and the underlying cellular behaviours are also profoundly linked to disease states like cancer formation and metastasis . However, the mechanisms underlying tissue boundary formation are poorly understood: Successful formation of tissue boundaries requires a tight coordination between acquisition of cell fate and regulation of cellular properties responsible for morphogenesis, such as cell division, motility, polarity, and adhesion . It has been challenging to analyse how gene expression, cell lineages and cell movement coordinate in space and time.
The overarching goal of this project is to probe the in vivo mechanisms of tissue boundary formation using the zebrafish embryonic shield region as a model system. I will generate a dynamic atlas characterizing the (1) cellular and (2) molecular basis of boundary formation, and (3) identify key regulators and their mechanism in cell differentiation and morphogenesis during boundary formation. This region has been of long-standing interest because it corresponds to the Mangold-Spemann organizer, but only now has it become tractable as a model system to study tissue boundary formation between multiple diverse cell types through the advent of technological revolutions in live imaging (Aim 1), spatial transcriptomics (Aim 2) and genome editing (Aim 3)
