Paraxial-Fated Mesoderm Is Required for Neural Crest Induction inXenopusEmbryos

Abstract

Neural crest induction is thought to occur by a two-step process. Axially fated mesoderm induces neural plate, which is then recruited to neural crest by nonneural epidermal ectoderm at the neural plate border. This model suggests a rather indirect role for mesoderm in inducing neural crest. We extensively examined the role of mesoderm in neural crest induction by determining which types of mesoderm induce neural crest cells in Xenopus embryos. We found that noggin-dorsalized ventral marginal zone (VMZ) explants differentiate as melanocytes in the absence of axial mesoderm. Dorsalized VMZ is also a potent inducer of melanocytes when juxtaposed to animal cap ectoderm in recombinant explants. Dorsalized VMZ is analogous to the dorsal-lateral marginal zone (DLMZ) region of the embryo. Neural crest-inducing activities of gastrula stage DLMZ and dorsal marginal zone (DMZ) were also compared in recombinant explants. DLMZ was a stronger inducer of neural crest than was DMZ; DLMZ induced high levels of XSlug expression and melanocyte formation in recombinants, whereas DMZ weakly induced neural crest. In whole embryos lacking DLMZ, XSlug expression and melanocyte formation were significantly reduced; in contrast, no significant reduction of XSlug expression or melanocyte formation was seen in embryos lacking a DMZ. These results suggest that paraxial-fated mesoderm plays a central role in neural crest formation by inducing a novel type of lateral neural plate. This lateral neural plate is then recruited to neural crest by adjacent nonneural epidermal ectoderm.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…The preliminary evidence for a role of mesoderm as source of inductive signals comes from the path-breaking experiment of Raven and Kloos who were able to obtain NC derivatives in salamander embryos by grafting paraxial and lateral mesoderm into the ectoderm of blastocoel (Raven and Kloos, 1945). Further studies show that removal of paraxial mesoderm in Xenopus embryos causes reduced expression of Snail2 and recombination of ectoderm explants with paraxial mesoderm can activate Snail2 expression and induce melanocyte formation (Bonstein et al, 1998, Marchant et al, 1998. Taken together these data provide the support for the necessity of inductive interactions between neural plate, non-neural ectoderm and paraxial mesoderm for proper formation of NC cells.…”

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

“…117 Subsequently, Hong et al 118 reported that FGF acts by inducing Wnt8 in paraxial mesoderm, which in turn acts to induce neural crest, while Wu et al 119 reported that Wnt signaling could induce neural crest even when FGF signaling was blocked. A recent analysis of mesoderm-neural crest interactions 9 confirmed and extended Bonstein's 39 original finding that dorsal lateral mesoderm was necessary and sufficient to induce neural crest from animal cap (ectoderm) explants. An analysis of their observation reveals a number of unanswered questions, associated with the dynamic and co-dependent nature of the embryonic system.…”

“…Ragland and Raible 38 reported that signals from mesoderm "are dispensable for zebrafish neural crest induction," although not for their normal migration (see below). This was a surprising finding, given the report by Bonstein et al 39 that paraxial mesoderm, which corresponds to the dorsal lateral marginal zone of the late blastula/early gastrula stage embryo, is required for neural crest induction in Xenopus. This discrepancy may represent a species difference; however, we side with the notion that the mesoderm is generally important for neural crest specification.…”

Signaling pathways and tissue interactions in neural plate border formation

“…Co-culture of na€ ıve ectoderm with dorso-lateral marginal zone (DLMZ) mesoderm induced the expression of NC marker genes including snail2/slug, foxD3 and sox9. 4,[12][13][14] Consistently, Xenopus embryos in which the dorsolateral mesoderm has been experimentally removed fail to develop NC as indicated by the lack of snail2/slug expression at neurula stage and the failure to form NC derivatives such as melanocytes. 12,13 The cross-species conservation of the mechanisms underlying these inductive capacities was demonstrated by explant assays performed with inducing tissue from posterior nonaxial mesoderm from chick and responding ectoderm from Xenopus.…”