Edn1/Ednra signaling in Xenopus neural crest development

MANUEL J. AYBAR

Los Cocos, Córdoba

Workshop; International Workshop “Latest concepts in Developmental Biology”; 2006

  The neural crest is a multipotent group of cells that arises at the neural plate border and migrates throughout the embryo to give rise to a wide variety of cell types including peripheral and enteric neurons and glia, smooth muscle, craniofacial cartilage and bone, endocrine and pigment cells. Recent studies in chick, zebrafish and amphibian embryos have demonstrated the importance of BMP4, Wnt, FGF, Notch/Delta and retinoic acid signaling in the initial induction of the neural crest. In last years, it has been found that the Endothelin1/Endothelin Receptor A (Edn1/Ednra) cell signaling pathway participates during development in the morphogenesis of cranial structures in mouse, chick and zebrafish embryos. Here we provide evidence of a major role for Edn1/Ednra pathway in the neural crest developmental processes of the amphibian embryo. We found out that Ednra is expressed from early neurula stages (stage 13) in the neural plate border corresponding to the prospective neural crest. This early expression pattern is unique and it is not conserved in other vertebrate embryos. At later stages, Ednra expression was found in all migratory neural crest cells, while in the postmigratory neural crest cells Ednra was located in branchial arches and the otic vesicle. To investigate the role of Edn1/Ednra pathway during development we followed different gain- and loss-of- function approaches. Our results demonstrated that the overexpression of Ednra mRNA induced the expression of the neural crest markers, while the knockdown of Ednra using antisense morpholino oligonucleotides showed that the Edn1/Ednra signaling is required for neural crest induction. The temporal requirements of Edn1/Ednra signaling were analyzed both in vivo and in vitro by grafting beads soaked in Edn1 ligand or in the specific inhibitor of Ednra named BQ123. Our results showed that Edn1/Ednra signaling is involved in the maintenance of specification and migration of neural crest, and in the induction of melanocytes. Additionally, we analyzed the participation of Edn1/Ednra pathway in the control of apoptosis and cell proliferation in the neural crest. Altogether, our results support the Edn1/Ednra signaling as a key player in the molecular mechanisms that control the neural crest induction, migration, and the formation of neural crest derivatives in Xenopus.