Chapter 15 - Lessons from the Zebrafish Lateral Line System

Abstract

The Posterior Lateral Line system (PLL) in zebrafish is a remarkably effective model system for understanding how interactions between cells and integration of input from multiple signaling systems regulates pattern formation, morphogenesis, growth, and collective migration during the self-organization of tissues during development. The PLL is established by the PLL primordium (PLLp), a collection of about 100 cells, which migrates from the ear to the tip of the tail periodically depositing sensory organs called neuromasts. ligands, expressed in response to Wnt signaling in a leading domain, establish center-biased FGF (Fibroblast Growth Factor) signaling centers in an adjacent trailing domain to coordinate periodic formation of nascent neuromasts or protoneuromasts within the migrating PLLp. FGF signaling initiates center-biased atoh1a expression in protoneuromasts, giving them the potential to become sensory hair cell progenitors. Lateral inhibition mediated by Notch signaling operates in this context to restrict atoh1a expression to the central cell, specifying it as a sensory hair cell progenitor, while neighboring cells, in which atoh1a has been suppressed, become support cells. Polarized expression of chemokine receptors, Cxcr4b and Cxcr7b, in leading and trailing cells, respectively, determines directed migration of the PLLp along a path defined by the relatively uniform expression of the chemokine ligand, Cxcl12a. Cxcl12a ligand binds the Cxcr4b receptor to engage the G protein coupled signaling pathway and determine migratory behavior of leading cells, while Cxcr7b receptors in trailing cells play a key role in reducing availability of the Cxcl12a to Cxcr4b in trailing cells.