BMP and non-canonical Wnt signaling are required for inhibition of secondary tail formation in zebrafish

Abstract

SUMMARYThe role of bone morphogenetic protein (BMP) signaling in specifying cell fate in the zebrafish tailbud has been well established. In addition to a loss of ventral tissues, such as ventral tailfin and cloaca, some embryos with compromised BMP signaling produce an additional phenotype: a ventrally located secondary tail containing both somitic muscle and notochord. This phenotype has been proposed to reflect a fate-patterning defect due to a change in a hypothesized BMP activity gradient. Here, we show that a defect in morphogenetic movements, not fate patterning, underlies the formation of secondary tails in BMP-inhibited embryos. Our data indicate that BMP signaling is activated in the ventroposterior tailbud to promote cell migration during tailbud protrusion, and that defective migration of these cells in BMP mutants ultimately leads to bifurcation of the caudal notochord. Additionally, we show that non-canonical Wnt signaling is also required for proper tail morphogenesis, possibly by maintaining cohesion of notochord progenitors by regulation of cadherin localization. We propose a model in which BMP and the noncanonical Wnt pathway regulate tail morphogenesis by controlling cell migration and cell adhesion within the tailbud.

The zebrafish tailbud contains two independent populations of midline progenitor cells that maintain long-term germ layer plasticity and differentiate based on local signaling cues

“…By contrast, floor plate is continuous in the primary tail anterior and posterior to the ectopic tail (Fig. S1), and previous work has demonstrated that neural tissue, including floor plate, is never found in the ectopic tail (Gebruers et al, 2013;Pyati et al, 2005;Yang and Thorpe, 2011). These results indicate that embryos with ectopic tails undergo a separation of the dorsal and ventral MPC populations, and that ventral MPC derivatives (notochord and hypochord) populate the ectopic tail and dorsal MPC derivatives (notochord and floor plate) reside in the primary tail.…”

“…The same phenotype occurs after loss of non-canonical Wnt signaling, and in both cases the posterior notochord is bifurcated along the dorsalventral axis, with one part in the normal notochord domain and the other extending into the ectopic ventral tail (Gebruers et al, 2013;Pyati et al, 2005;Yang and Thorpe, 2011). This phenotype arises from defective cell migration (Yang and Thorpe, 2011). We showed that embryos with ectopic ventral tails exhibit a separation of the two MPC populations, with the ectopic tail containing descendants of the ventral MPCs, including hypochord and notochord, whereas the primary midline posterior to the ectopic tail contains only descendants of the dorsal MPCs (floor plate and notochord).…”

“…The ectopic tail frequently contains notochord cells (Gebruers et al, 2013;Pyati et al, 2005;Yang and Thorpe, 2011). We reasoned that this might represent a splitting of the dorsal and ventral MPC populations, which would provide further evidence for the existence of the two MPC populations that we identified by genetic and lineage tracing-based methods.…”

“…We hypothesize that BMP and non-canonical Wnt signaling are required for the proper migration and/or coalescence of the two independent MPC populations. Ectopic tails also contain somitic tissue (Pyati et al, 2005;Yang and Thorpe, 2011), which may be due to the organizer activity of the tailbud, as observed in frog embryos (Gont et al, 1993). Alternatively, this might be due to respecification of some of the ventral MPCs as they enter a different signaling environment, similar to that observed upon expanding msgn1 expression into the tailbud MPCs.…”

“…In zebrafish, loss of BMP signaling during late gastrulation or early somitogenesis stages results in a partially penetrant phenotype of an ectopic tail on the ventral side of the posterior embryo (Pyati et al, 2005;Stickney et al, 2007;Yang and Thorpe, 2011). The same phenotype occurs after loss of non-canonical Wnt signaling, and in both cases the posterior notochord is bifurcated along the dorsalventral axis, with one part in the normal notochord domain and the other extending into the ectopic ventral tail (Gebruers et al, 2013;Pyati et al, 2005;Yang and Thorpe, 2011). This phenotype arises from defective cell migration (Yang and Thorpe, 2011).…”