MORPHOGENESIS · Coordinating cell differentiation and morphogenesis in a migrating tissue

The formation of many organs involves the migration of cells in groups of different size and shape. Interestingly, these collective movements are also involved in metastatic processes in a variety of cancers. Yet how cells coordinate their behavior with that of their neighbors within moving groups is poorly understood. We use the posterior lateral line (pLL) of the Zebrafish as a model system to investigate how cell shape changes, differentiation, and directed tissue migration are functionally coupled during organ formation. During the second day of development of the zebrafish embryo, a group of about 100 cells, the pLL primordium (pLLP) migrate on both sides of the fish. As they migrate, subgroups of cells at the back assemble into rosette-like assemblies, the proneuromasts, that are progressively deposited behind and differentiate into the mechanosensory organs of the lateral line. Zebrafish embryos present the enormous advantage of being transparent at the beginning of their development. This, combined to superficial migration of the pLLP just under the skin makes this tissue an ideally suited model system for imaging complex morphogenetic movements in vivo. We have recently shown that the cellular rosettes are apically constricted epithelial clusters, radially organized around an fgf ligand-expressing cell. We further demonstrated that the FGF signaling pathway is required for cells to assemble into rosettes, and that in turn rosettes formation is a prerequisite for coordinated migration of the primordium. In order to understand how FGF signals drive cellular rosettes assembly, we will combine live cell imaging to genetics, mosaic analysis, pharmacological treatments and mathematical modeling to: (i) dissect the intracellular cascade downstream of Fgf (ii) perturb the morphogenetic process of rosettes assembly (iii) understand how fgf ligand expression gets restricted to single rosette-nucleating cell.