The zebrafish lateral line is an insightful system for studies of cellular development as it displays evolutionarily-conserved developmental mechanisms ranging from progenitor migration, neural differentiation and planar cell polarity to sensory transduction. Furthermore, the lateral line is thought to have evolved into sensory structures of the cochlea and inner ear in drier vertebrates, making it an organ of broad interest for developmental neurobiology. The posterior lateral line is a mechanosensory organ running along the body and tail of fish and amphibians. It is built during early development through coordinated cell migration, proliferation, epithelial morphogenesis and differentiation of a group of about one hundred cells forming the pLL primordium. The pLL PF-4217903 primordium arises from placodal cells that undergo partial epithelial-mesenchymal transition and acquire migratory properties. As the primordium migrates towards the tail along the myoseptum, cells in the trailing zone of the primordium become organized into rosette-like epithelial structures that mature into proneuromasts. These cells differentiate as the accessory and hair cells of the 6–7 mature neuromasts of the primary pLL. When the primordium reaches the end of the tail, it fragments into a few terminal neuromasts. Thus, the timing of neuromast deposition and the underlying molecular mechanisms of its regulation are critical for the development of this organ. The migration of the primordium and the formation of the neuromasts is coordinated by Wnt and Fgf signaling. Through a feedback mechanism, Wnt/b-catenin signaling is restricted to the leading zone of the primordium and Fgf signaling occurs in the trailing zone. These localized activities maintain the polarized activation of two chemokine receptors: cxcr4b is expressed in the leading zone while cxcr7b is restricted to the trailing zone. The differential expression of cxcr4b and cxcr7b is essential for directed collective migration of the primordium cells. However, the mechanisms downstream of these receptors that convey their actions are unclear. The ubiquitin ligase ITCH has been shown to influence signaling downstream of several important receptors. In particular, ITCH recognizes and down-regulates several SH3-domain proteins, which have been shown to limit epidermal growth factor receptor internalization and signaling. Although no direct link has been established between ITCH and FGF signaling, ITCH targets proteins involved in receptor tyrosine kinase internalization like CBL and SH3GL2. ITCH directly interacts with ligand-activated CXCR4 and promotes its ubiquitylation at the plasma membrane, which is important for the regulation of CXCR4 trafficking and signaling. In human cell lines, ITCH depletion significantly attenuates CXCR4-induced ERK-1/2 activation and modestly increases CXCR4 surface levels.