A new role for the Endothelin-1/Endothelin-A receptor signaling during early neural crest specification.
The neural crest is induced at the border of the neural plate in a multistep process by signals emanated from the epidermis, neural plate and mesoderm. In this work we show for the first time the existence of a neural crest maintenance step which is dependent on signals released from the mesoderm. We identified Endothelin-1 (Edn1) and its receptor (Ednra) as key players of this signal and we show that Edn1/Ednra signaling is required for maintenance of the neural crest by a dual mechanism of cell specification and cell survival. We show that: (i) Ednra is expressed in prospective neural crest; (ii) loss-of-function experiments with antisense morpholino or with specific chemical inhibitor suppress the expression of early neural crest markers; (iii) gain-of-function experiments expand the neural crest territory; (iv) epistatic experiments show that Ednra/Edn1 is downstream of the early neural crest gene Msx1 and upstream of the late genes Sox9 and Sox10; and (v) Edn1/Ednra signaling inhibits apoptosis and controls cell specification of the neural crest. Together, our results provide insight on a new role of Edn1/Ednra cell signaling pathway during early neural crest development.
Bonano
Marcela
M
Departamento de Biología del Desarrollo, INSIBIO (CONICET-Universidad Nacional de Tucumán), Chacabuco 461, T4000ILI - San Miguel de Tucumán, Tucumán, Argentina.
Tríbulo
Celeste
C
De Calisto
Jaime
J
Marchant
Lorena
L
Sánchez
Sara S
SS
Mayor
Roberto
R
Aybar
Manuel J
MJ
D000818:Animals; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000502:physiology; D004627:Embryonic Induction / Q000235:genetics*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008954:Models, Biological; D009432:Neural Crest / Q000378:metabolism / Q000502:physiology*; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014981:Xenopus / Q000196:embryology / Q000235:genetics / Q000378:metabolism
D019332:Endothelin-1; D044022:Receptor, Endothelin A