miR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression

Yehonatan Epstein, Noam Perry, Marina Volin, Maayan Zohar-Fux, Rachel Braun, Lilach Porat-Kuperstein and Hila Toledano ()
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Yehonatan Epstein: University of Haifa
Noam Perry: University of Haifa
Marina Volin: University of Haifa
Maayan Zohar-Fux: University of Haifa
Rachel Braun: University of Haifa
Lilach Porat-Kuperstein: University of Haifa
Hila Toledano: University of Haifa

Nature Communications, 2017, vol. 8, issue 1, 1-9

Abstract: Abstract Ageing is characterized by a decline in stem cell functionality leading to dampened tissue regeneration. While the expression of microRNAs across multiple species is markedly altered with age, the mechanism by which they govern stem cell-sustained tissue regeneration is unknown. We report that in the Drosophila testis, the conserved miR-9a is expressed in germline stem cells and its levels are significantly elevated during ageing. Transcriptome and functional analyses show that miR-9a directly regulates the expression of the adhesion molecule N-cadherin (N-cad). miR-9a null mutants maintain a higher number of stem cells even in the aged tissue. Remarkably, this rise fails to improve tissue regeneration and results in reduced male fertility. Similarly, overexpression of N-cad also results in elevated stem cell number and decreased regeneration. We propose that miR-9a downregulates N-cad to enable adequate detachment of stem cells toward differentiation, thus providing the necessary directionality toward terminal differentiation and spermatogenesis.

Date: 2017
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DOI: 10.1038/s41467-017-00485-9

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