CONICET | Buscador de Institutos y Recursos Humanos

Theneural crest (NC) is a stem-cell like embryonic population that is crucial for embryodevelopment. The cells of the NC differentiate and migrate along the embryo togive rise to different cellular types, such as sensitive neurons and glia, cartilage,bone, connective tissue, neuroendocrine and pigmentary cells. In our lab we havedemonstrated that Indian Hedgehog signaling pathway plays a key role in Xenopus laevis neural crest formation,specification and migration. The Gli2 transcription factor is the main effectorof this signaling pathway. In this work we have established the detailedexpression pattern of gli2 transcriptsfrom early neurula to tailbud stage. We show that they are expressed in theprospective neural crest during neurula stage and in the otic vescicle andbranchial arches during later stages. Overexpression of the gli2 mRNA produced an increase in theexpression of neural crest specific gene markers, such as pax3, snail2 and foxd3, evidenced by in situ hybridization and semiquantitative RT-PCR. In addition, thegain of function of gli2 diminished theapoptotic state of NC cells. The specific knock-out of gli2 function by the use of an antisense morpholino oligonucleotideand by pharmacological inhibition by using the GANT61 inhibitor produced adecrease in the expression of the above mentioned NC markers. Theloss-of-function of gli2 alsoaffected the migration of the neural crest cells and produced an alteration inthe formation of NC derivatives such as the craniofacial cartilages and melanocytes.The epistatic analysis showed that gli2 couldact downstream of the Endothelin receptor A signaling and the Eg5 atypicalkinesin gene during NC induction. Taken together, these results indicate anessential role of gli2 in the geneticnetwork that controls the formation of neural crest cells and the properformation of neural crest derivatives.

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