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| Author(s): |
Mateus Augusto de Andrade Souza
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2015-12-03 |
| Examining board members: |
Fabio Papes;
Katlin Brauer Massirer;
Isaias Glezer
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| Advisor: | Fabio Papes |
| Abstract | |
In mammals, the olfactory sensory neurons (OSNs) are located inside the nasal cavity, but they are directly exposed to the external environment. Taking advantage of the respiratory flux, this location favors the access to the chemical stimuli presented by the environment. On the other hand, it leads OSNs to be continually damaged by pathogens and toxic substances carried by the inhaled air. However, the persistence of neuronal progenitors in the olfactory epithelium makes the constant reposition of the OSNs possible. This unique ability of regeneration makes the Olfactory System one of the few sites of neurogenesis throughout the adult life. Olfactory regeneration has attracted the attention scientific community because of its potential as a model of study of the Nervous System and application in the treatment of neurodegenerative diseases. A great amount of knowledge has been accumulated about the transcription factor dynamics that follows the differentiation of neuronal progenitors into OSNs. However, there is a great gap about other elements that could coordinate this process, such as chromatin modulator factors. In this scenario, we decided to study the Polycomb Group (PcG) proteins, a transcription control machinery involved in chromatin structure organization. In the present study, selected PcG genes were molecular and functionally analyzed in the mouse main olfactory epithelium (MOE). Using in situ hybridization assays, we characterized the expression of six PcG genes. Five of them were shown to be expressed throughout the MOE (Cbx2, Cbx4, Phc2, Ezh1, Bcl6), while one (Ezh2) was found only in the basal layers of this epithelium. Using colocalization strategies, we proved that Ezh2 gene is expressed exclusively in the olfactory progenitor cells, where the differentiation process begins, and in part of the newly differentiated OSNs that are still not functional. It was the first time that a PcG gene expression profile was finely analyzed in the Olfactory System. This interesting expression profile presented by Ezh2 suggested a possible involvement with the MOE neuronal progenitor differentiation. For this functional investigation, we used MOE¿s neuronal regeneration after specific injuries as an experimental tool. For this purpose, the MOE was chemically damaged by the compound dichlobenil, which causes a great loss of OSNs, stimulating proliferation and differentiation of neuronal progenitor cells, leading to the repopulation of the damaged tissue. Next, mice received by intranasal route the pharmacological inhibitor GSK126, which blocks EZH2 protein activity. The observation of the MOE regeneration that followed showed us that GSK126 application resulted in an increased number of OSNs, improving MOE regeneration. Interestingly, this increase was also found in intact MOEs, pointing that GSK126¿s effects do not depend on previous olfactory injuries. By this molecular and functional investigation, we aimed at a better understanding of olfactory neuronal differentiation, and we targeted the PcG proteins as relevant elements to this process (AU) | |
| FAPESP's process: | 13/03372-6 - Molecular and functional investigation of Polycomb Group proteins and their involvement in olfactory neurogenesis |
| Grantee: | Mateus Augusto de Andrade Souza |
| Support Opportunities: | Scholarships in Brazil - Master |