The role of Endothelin-1/Endothelin Receptor A signaling in neural crest specification and cell survival

MARCELA BONANO; CELESTE TRÍBULO; SARA SÁNCHEZ; ROBERTO MAYOR; MANUEL J. AYBAR

Cancún, México

Congreso; First Panamerican Congress in Developmental Biology (66th Meeting Society for Developmental Biology,USA; 8th Meeting Sociedad Mexicana de Biologia del Desarrollo y 3rd Meeting Latin American Society for Developmental Biology); 2007

SDB (USA) y LASDB

The neural crest (NC) is a multipotent cell population that gives rise to different tissues after extensive migration along the vertebrate embryo. In the frog Xenopus laevis, the NC is specified in the ectoderm from late gastrula stage by interactions between different signals emanated from the epidermis, neural plate and mesoderm. It has been proposed that neural crest induction is a multi step process, but so far these different steps are not completely understood. In this work, we show for the first time the existence of a NC maintenance step which occurs after the initial induction of NC, and that is dependent on Edn1 signal released from the mesoderm underlying the neural crest at the neurula stage. We have cloned Xenopus Preproendothelin-1 and ECE-1 homologues, and the analysis of the expression patterns confirmed that mesoderm is a source of Edn1 signal. Gain- and loss-of-function approaches, the use of a specific Ednra inhibitor, and embryological experiments show that Edn1/Ednra signaling is required for neural crest development through a dual mechanism that controls neural crest specification and cell survival. The blocking of the apoptosis by a Slug-inducible construct in NC explants indicates that the control of NC specification by Edn1/Ednra signaling is independent from the control of cell survival. In addition, the epistatic analysis shows that Ednra is downstream Msx1 and upstream Sox9 and Sox10 in the NC specification cascade. Our results provide insight on a new role of Edn1/Ednra cell signaling pathway during NC development.Xenopus laevis, the NC is specified in the ectoderm from late gastrula stage by interactions between different signals emanated from the epidermis, neural plate and mesoderm. It has been proposed that neural crest induction is a multi step process, but so far these different steps are not completely understood. In this work, we show for the first time the existence of a NC maintenance step which occurs after the initial induction of NC, and that is dependent on Edn1 signal released from the mesoderm underlying the neural crest at the neurula stage. We have cloned Xenopus Preproendothelin-1 and ECE-1 homologues, and the analysis of the expression patterns confirmed that mesoderm is a source of Edn1 signal. Gain- and loss-of-function approaches, the use of a specific Ednra inhibitor, and embryological experiments show that Edn1/Ednra signaling is required for neural crest development through a dual mechanism that controls neural crest specification and cell survival. The blocking of the apoptosis by a Slug-inducible construct in NC explants indicates that the control of NC specification by Edn1/Ednra signaling is independent from the control of cell survival. In addition, the epistatic analysis shows that Ednra is downstream Msx1 and upstream Sox9 and Sox10 in the NC specification cascade. Our results provide insight on a new role of Edn1/Ednra cell signaling pathway during NC development.