Investigating microRNAs during cardiac development in the chick

The heart, the first organ to function in developing vertebrate embryos1, is affected by congenital defects in roughly 1% of the worldwide human population. These abnormalities frequently require treatment for the entire lifespan of the affected individual2,3. microRNAs are an exciting class of non-coding regulatory genes that are known to be essential for the heart development of many organisms4,5. A miRNA becomes incorporated into the miRNA-induced silencing complex, which binds to a target mRNA transcript and inhibits its translation. Dysregulation of miRNAs is associated with failing human hearts6. More than 2,500 mature human miRNAs are currently annotated, and with each miRNA predicted to potentially target several hundred transcripts, the further study of these molecules is vital for the complete understanding of cardiac biology. A miRNA expression profile in the chick heart, a model of human heart development, over several stages of embryonic development was generated by next generation sequencing. Two novel chick miRNAs were discovered, and 31 known animal miRNAs not yet annotated in the chick genome were discerned. The predicted targets of three miRNAs thought to be essential for heart development, miR-130, miR-138, and miR-499, were examined in vitro. Twelve genes were confirmed as targets of at least one of these three miRNAs by luciferase reporter assay, including genes in the Wnt signalling pathway which is essential at specific stages of heart development7. The roles of miR-1, known to be indispensable for heart formation and function, were also studied in the developing chick heart. Two targets of miR-1, FZD7 and RARβ, had been identified in vitro8. This study showed that inhibition of miR-1 in the HH14 chick resulted increased FZD7 and RARβ protein levels, as well as in delayed development, possibly due to a loss of inhibition of canonical Wnt signalling in the epicardium.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2014

Author dc:creator

• Mccormick, Dominique

Language dc:language

en