Indian hedgehog signaling is required for proper formation, maintenance and migration of Xenopus neural crest

TRISTÁN H. AGÜERO; JUAN P. FERNÁNDEZ; GUILLERMO VEGA LÓPEZ; CELESTE TRÍBULO; MANUEL J. AYBAR

DEVELOPMENTAL BIOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2012 vol. 364 p. 99 - 113

0012-1606

The neural crest induction is the result of combined action at the neural plate border of FGF, BMP, and Wnt signals from the neural plate, mesoderm and nonneural ectoderm. In this work we show that the expression of Banded hedgehog and members of the Hedgehog pathway occurs at the prospective neural fold, in the premigratory and migratory neural crest. We performed a functional analysis that revealed the requirement of Bhh signaling in the neural crest development. During the early steps of neural crest induction loss of function experiments with antisense morpholino or locally grafted cyclopamine- loaded beads suppress the expression of early neural crest markers concomitant with the increase in neural and epidermal markers. We show that changes in Bhh activity produce no alterations neither in cell proliferation nor apoptosis suggesting that this signal involves cell fate decisions. A temporal analysis shows that hedgehog is continuously required not only in the early and late specification but also during the migration of the neural crest. We also established that the mesodermal source of Bhh is important in the maintenance of specification and to support the migratory process. By a combination of embryological and molecular approaches our results demonstrate that Bhh signaling drives in the migration of neural crest cells by autocrine or paracrine mechanisms. Finally, the abrogation of Bhh signaling strongly affected only the formation of cartilages derived from the neural crest, while no effects were observed in melanocytes. Taken together, our results provide insights on the role of Bhh cell signaling pathway during early steps of neural crest development.