Itch Is Required for Lateral Line Development in Zebrafish

Abstract

The zebrafish posterior lateral line is formed during early development by the deposition of neuromasts from a migrating primordium. The molecular mechanisms regulating the regional organization and migration of the primordium involve interactions between Fgf and Wnt/-catenin signaling and the establishment of specific cxcr4b and cxcr7b cytokine receptor expression domains. Itch has been identified as a regulator in several different signaling pathways, including Wnt and Cxcr4 signaling. We identified two homologous itch genes in zebrafish, itcha and itchb, with generalized expression patterns. By reducing itchb expression in particular upon morpholino knockdown, we demonstrated the importance of Itch in regulating lateral line development by perturbing the patterns of cxcr4b and cxcr7b expression. Itch knockdown results in a failure to down-regulate Wnt signaling and overexpression of cxcr4b in the primordium, slowing migration of the posterior lateral line primordium and resulting in abnormal development of the lateral line.

Predicted molecular signaling guiding photoreceptor cell migration following transplantation into damaged retina

“…Common nuclear elements between NSR and RPE cone PPC signaling pathways ( Fig. 1c,d ) include signal transducer and activator of transcription 2 (STAT2) and E3 ubiquitin-protein ligase Itchy homolog (ITCH), both associated migratory signaling 74 75 . This data demonstrates that downstream signaling pathways active in PPC migration are conserved across different tissue types and biologic processes.…”