Identification of neural crest competence territory: Role of Wnt signaling

Abstract

In recent years, research on neural crest induction has allowed the identification of several molecules as candidates for neural crest inducers. Although many of these molecules have the ability to induce neural crest in different assays, a general mechanism of neural crest induction that includes a description of the tissues that produce the inductive signals and the time and steps in which this process takes place remains elusive. To better understand the mechanism of neural crest induction, we developed an assay that has been used previously by Nieuwkoop to study anterior-posterior pattern of the neural plate. Folds of competent ectoderm were implanted in different positions of a young neurula embryo, and the induction of neural crest was analyzed using the expression of the neural crest marker Xslug. We identified a very localized region of the early neurula where it is possible to get neural crest induction, whereas all of the regions tested showed a clear induction of the neural plate marker Xsox2. These results indicate that there is a region in the embryo with the appropriate combination of signals needed to induce neural crest cells; we called this region the neural crest competence territory. In addition, our results show that neural crest induction is always accompanied by neural plate induction, but there are many cases where neural plate was induced without neural crest. These results support the model in which the neural crest is induced by an interaction between neural plate and epidermis, but they also suggest that additional signals are required. By making grafts of different sizes and implanting them in the epidermis or the neural plate, we concluded that one of the inductive signals is produced in the dorsal region of the embryo and travels into the ectoderm. Finally, by performing gain-and loss-of-function of Wnt signaling experiments, we show that this pathway plays an important role not only in neural crest induction but also in the specification of the neural crest competence territory. Developmental Dynamics 229: 109 -117, 2004.

The Snail genes as inducers of cell movement and survival: implications in development and cancer

“…These data suggest that cooperation occurs between WNT signalling and other Snail-induced signalling pathways, such as FGF, in the triggering of the EMT. This cooperation has been already highlighted in several developmental systems, in particular, in the mesoderm and the neural crest (Ciruna et al, 2001;Bastidas et al, 2004;Meulemans and BronnerFraser, 2004). For example, when Snail1 activity is maintained, E-cadherin is repressed and is therefore not available to bind β-catenin and form adherens junctions.…”

Essential role of non-canonical Wnt signalling in neural crest migration

“…1), indicating that non-canonical signalling does not participate in neural crest induction. Another Dsh mutant, dd1 is also able to block neural crest migration (data not shown), but it also interferes with the canonical Wnt pathway , and as a consequence reduces neural crest induction (Bastidas et al, 2004). Overexpression of Wnt11 dramatically affected neural crest migration, but also affected neural crest induction in some cases.…”

“…Embryos were injected with 1 ng of Wnt11 mRNA. To have a naive ectoderm expressing Wnt11, the animal cap was dissected at stage 9, but because at this stage the ectoderm is competent to respond to neural crest induction, the animal cap was cultured in vitro under a coverslip until the equivalent of stage 14, when the competence for neural crest induction has been lost (Bastidas et al, 2004;Mancilla and Mayor, 1996). With the purpose of generating a localized source of Wnt11 signalling, the cultured ectoderm was grafted into the neural plate region of a normal stage 14 embryo, but adjacent to the prospective neural crest cells, and neural crest migration was analyzed.…”

“…We propose that Wnt11 can trigger a cellular activity required for cell movement during delamination and/or cell migration, and that the crest cells require additional cues to translate this into an effective cell migration. The possibility that neural crest was induced in the graft is ruled out, as competence for neural crest induction is lost at the stage at which the tissue was transplanted (Mancilla and Mayor, 1996;Bastidas et al, 2004). It is still possible that Wnt11 promotes cell proliferation (Ouko et al, 2004), although this seems unlikely as cell numbers in our in vitro cultures did not increase after stimulating Wnt11 signalling.…”

Diversity in the molecular and cellular strategies of epithelium-to-mesenchyme transitions: Insights from the neural crest

“…However, so far, this question remains elusive as it is only relatively recently that the fate map of NC cell progenitors has been established for the anterior regions of the embryo. 23, 50 We still do not known with precision how prospective NC cells are generated in more caudal regions, and particularly in regions of secondary neurulation. Likewise, how NC progenitors are driven to the dorsal aspect of the neural tube during formation of the neural keel in the zebrafish has not been described with precision.…”