Palardy, G.; Yoo, K.-w.; Fatma, S.; Mukherjee, A.; Wang, C.; Ravi, P.; Chitnis, A. B.

Periodic formation of protoneuromasts within the migrating zebrafish Posterior Lateral Line primordium serves as a model for understanding steps that determine the self-organization of organ systems in development. Protoneuromast formation is initiated by Fgf signaling at the trailing zone of the migrating primordium in response to Fgfs produced by Wnt active cells in a leading zone. Progressive restriction of an initially broad Wnt signaling domain to a smaller leading zone allows new Fgf signaling-dependent protoneuromasts to form in the wake of the shrinking Wnt system. We show Sox2 and Sox3 are expressed in nascent and maturing protoneuromasts in a trailing part of the primordium in a pattern that is complementary to Wnt activity in a leading domain, where Sox1a, is expressed. Together, these SoxB1 factors help inhibit Wnt signaling to determine effective maturation of trailing protoneuromasts and the timely deposition of stable neuromasts. Using dkk1b and atoh1b to monitor initiation and subsequent maturation of protoneuromasts, respectively, we show how Wnt signaling regulates the pace of protoneuromast maturation in the migrating primordium, and how its inhibition by SoxB1 family members ensures maturation and deposition of stable neuromasts. Together, our observations define three steps in the periodic formation of neuromasts: first, polarization of Wnt activity in the primordium; second, pattern forming step that determines periodic formation of protoneuromasts in the context of polarized Wnt activity; and third, inhibition of Wnt signaling, which is essential for stabilizing nascent neuromasts formed in the earlier pattern forming stage.