WNT/β-catenin signaling regulates multiple aspects of lateral line morphogenesis

During development, groups of cells in the embryo must organize into precise morphologies required for the function of tissues and organs to enable the survival of organisms. This morphogenesis requires the coordinated regulation of basic cellular behaviors such as migration, cell shape changes and cell proliferation. Cell-cell signaling is required to orchestrate basic cellular behaviors in space and in time ensuring that these behaviors contribute to morphogenesis. Misregulated morphogenic signaling is associated with human disease. Understanding the cell-cell signaling interactions that regulate morphogenic cell behavior is a fundamental biological question. Zebrafish primary posterior lateral line (lateral line) development is an excellent basic model of morphogenesis. The lateral line emerges from a migrating primordium that travels as a cohesive, multicellular collective from the head to the tip of the tail. Prosensory organs are formed within in the migrating primordium and deposit from its trailing edge to generate a single row of mechanosensory organs distributed along the A-P axis of the trunk. Migration of the primordium depends on the interaction of the guidance molecule cxcl12a, expressed along the presumptive migratory path, and the receptors cxcr4b and cxcr7b. cxcr4b is expressed broadly expressed in the migrating primordium and cxcr7b is expressed exclusively in trailing and iv deposited cells. Both receptors are necessary for directed migration of primordium cells. Prosensory organ formation is involves the apical constriction of cells to generate cohesive, rosette shaped clusters. Rosette morphogenesis does not occur in cells occupying the leading region of the primordium, which serves as a progenitor pool for further prosensory organ formation. Data presented in this dissertation show that Wnt/β-catenin signaling is a key coordinator of cellular behaviors that underlies lateral line morphogenesis. First, Wnt/β-catenin signaling regulates the expression of chemokine receptors that underlie directional migration. Second, Wnt/β-catenin signaling restricts Fgf dependent proneuromast formation from the leading zone of the primordium maintaining this region as a progenitor zone and ensuring complete lateral line morphogenesis. Finally, Wnt/β-catenin signaling regulates proliferation of primordium cells and proliferation, in turn, influences the periodicity of proneuromast formation. Therefore, Wnt/β-catenin signaling represents a key coordinator of morphogenetic cell behaviors in during lateral line development.