Incoherent collective cell chemotaxis underlies organ dysmorphia in a model of branchio-oto-renal syndrome

Abstract

SUMMARYTissue remodeling presents an enormous challenge to the stability of intercellular signaling domains. Here we investigate this issue during the development of the posterior lateral line in zebrafish. We find that the transcriptional co-activator and phosphatase Eya1, mutated in the branchio-oto-renal syndrome in humans, is essential for the homeostasis of the Wnt/β-catenin and FGF morphogenetic domains during the collective migration of lateral-line primordial cells. Loss of Eya1 strongly diminishes the expression of Dkk1, expanding Wnt/β-catenin activity in the primordium, which in turn abrogates FGFR1 expression. Deficits in Eya1 also abolishes the expression of the chemokine receptor CXCR7b, disrupting primordium migration. These results reinforce the concept that morphogenetic domains in dynamically remodeling tissues are formed by cellular states maintained by continuous signaling.