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Epigenetic study in vivo of the role of retinoic acid in the regeneration of ciliate cells

16th national competition for scientific and technical research

Gene and regenerative therapy

Senior Researcher : Berta Alsina Español

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Research Centre or Institution : Universidad Pompeu Fabra-PRBB. Barcelona.


Ciliate cells are the mechanical receptor cells which receive and transmit acoustic stimuli. One of the most common sensory deficits in the population of industrialised countries is progressive hearing loss caused by acoustic damage or certain drugs, together with the impossibility of regenerating ciliate cells in mammals. This project has the aim of investigating the role of retinoic acid in the regeneration of the inner ear and the lateral line of the vertebrate zebra fish, for future use as a therapy in mammals. Functional experiments involving the manipulation of retinoic acid and FGF signalling routes are being combined with the in vivo visualisation of cellular regeneration and proliferation to understand the effect of retinoic acid on the regeneration of ciliated cells. To date it has been possible to prove that the synthesis of retinoic acid is activated in the support cells (those functioning as stem cells) under regeneration conditions. When regeneration is induced in ciliate cells by means of cellular ablation or orthotoxic harm, the blocking of retinoic acid signalling or of RAR receptors was found to suppress the de novo generation of ciliate cells, while the proliferation of support cells is inhibited. It has been possible to prove in vivo and in intact animals that new ciliate cells come from the support cells. Analysis of the epigenetic modifications in the chromatin under regeneration conditions using ChIP-seq is now commencing.

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