Functional analysis of Hairy genes in Xenopus neural crest development

GUILLERMO VEGA LÓPEZ; MANUEL J. AYBAR

Washington DC, USA

Congreso; 38th Annual Meeting of the Society for Neuroscience; 2008

Society for Neuroscience, USA

 It has been demonstrated that the yuxtacrine cell signaling pathway Notch/Delta is involved in the control of different developmental processes. One of these processes is the induction of neural crest in different vertebrate animal models. The genes of the Hairy family, encode transcription factors containing a bHLH DNA binding domain that are direct targets of Notch/Delta signaling in vertebrates and invertebrates. We have previously shown that Hairy1 is expressed in a narrow line at the border of neural plate and in the epidermis-neural crest boundary during early neurulation, and that Hairy2a and Hairy2b are both expressed in overlapping domains in the prospective neural crest territory. In order to analyze the role of Hairy genes during neural crest development we followed conditional gain- and loss-of-function approaches. We have prepared chimeric inducible proteins and their dominant negatives by fusing coding sequences to the ligand binding domain of human glucocorticoid receptor. The overexpression of in vitro transcribed mRNAs of chimeric inducible proteins and their dominant negatives, or the use of antisense oligonucleotides by microinjection into developing embryos showed that Hairy genes are involved in the neural crest cells induction and migration. The results show that Hairy genes could control the ectodermal specification directing cells to a neural crest cell fate, and that they also are able to control the neural crest cells survival. We also explored the ability of Hairy genes to induce neural crest cells in vitro by using an animal cap assay. The results showed that these genes lead to the expression of neural and neural crest marker genes. Our results provide insight about the role of three Hairy genes during neural crest development in Xenopus embryos and show that they could be functionally equivalent.