Functional genomics of micrornas in heart of vertebrates: using zebrafish as model organism

Author(s)

Pedro Gabriel Nachtigall

• Document type: Doctoral Thesis
• Press: Botucatu. 2017-03-16.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2017-02-23
• Advisor: Danillo Pinhal

Abstract

In vertebrates, heart is the first organ to form in the embryo and all subsequent events in the life of an organism depend on its function. Heart has acquired distinct morphological traits during vertebrate evolution, which leaded to distinct morphology traits in the living species. However, the molecular mechanisms that drive the differential morphology among these species remain uncharted. Taking into consideration the higher level of conservation of the genome among these species, we can infer that the differential expression of genes and regulators lead to the distinct pattern of heart morphology. MicroRNAs (miRNAs) are small molecules with an important role upon post-transcriptional regulation. These molecules have been shown essential for several cellular processes in vertebrates, including cardiac biology, but little is known about the roles of these small molecules in the development and evolution process of vertebrate’s heart. In the present study, we characterized the global expression of miRNAs in the heart of species from the five vertebrate groups, (fish, amphibians, reptiles, birds and mammals) and performed an evolutionary comparative analysis of miRNA expression signatures in order to bring novel insights about the molecular basis of heart phenotypic variability. RNA-seq was used to characterize miRNA expression profiles in the heart of 13 vertebrate species and deeply analyzed using bioinformatics. We found 32 miRNAs with conserved expression to all 13 species analyzed, indicating a conserved pathway of these miRNAs despite of the large divergence times isolating these organisms. GO analysis from 32 miRNAs in the human genome revealed that conserved miRNAs has functions on heart development and contraction rate, traits considered crucial for the differential morphology of the heart observed from fish to mammals. Furthermore, we validate the molecular interaction between miR-129 and Bmp4, important gene for the heart development. Moreoever, the functional analysis of interaction between miR-129 and Tbx factors will help elucidate the biological importance of miR-129 along heart development in vertebrates. (AU)

• FAPESP's process: 13/06864-7 - Functional analysis of microRNAs in cardiac development of fish species by RNA-Seq and reverse genetics
• Grantee: Pedro Gabriel Nachtigall
• Support Opportunities: Scholarships in Brazil - Doctorate