• PMID: 29187591
• Gene Name: DROSHA
• Condition: Gonadal sexual differentiation, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Gonadal sexual differentiation, Male infertility

MicroRNA dynamics at the onset of primordial germ and somatic cell sex differentiation during mouse embryonic gonad development

Fernández-Pérez D, Brieño-Enríquez MA, Isoler-Alcaraz J, Larriba E, Del Mazo J.

In mammals, commitment and specification of germ cell lines involves complex programs that include sex differentiation, control of proliferation, and meiotic initiation. Regulation of these processes is genetically controlled by fine-tuned mechanisms of gene regulation in which microRNAs (miRNAs) are involved. We have characterized, by small-RNA-seq and bioinformatics analyses, the miRNA expression patterns of male and female mouse primordial germ cells (PGCs) and gonadal somatic cells at embryonic stages E11.5, E12.5, and E13.5. Differential expression analyses revealed differences in the regulation of key miRNA clusters such as miR-199-214, miR-182-183-96, and miR-34c-5p, whose targets have defined roles during gonadal sexual determination in both germ and somatic cells. Extensive analyses of miRNA sequences revealed an increase in noncanonical isoforms on PGCs at E12.5 and dramatic changes of 3' isomiR expression and 3' nontemplate nucleotide additions in female PGCs at E13.5. Additionally, RT-qPCR analyses of genes encoding proteins involved in miRNA biogenesis and 3' nucleotide addition uncovered sexually and developmentally specific expression, characterized by the decay of Drosha, Dgcr8, and Xpo5 expression along gonadal development. These results demonstrate that miRNAs, their isomiRs, and miRNA machinery are differentially regulated and participate actively in gonadal sexual differentiation in both PGCs and gonadal somatic cells. CI - © 2018 Fernández-Pérez et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society. FAU - Fernández-Pérez, Daniel AU - Fernández-Pérez D AUID- ORCID: 0000-0002-1679-6555 AD - Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain. FAU - Brieño-Enríquez, Miguel A AU - Brieño-Enríquez MA AUID- ORCID: 0000-0002-8806-0918 AD - Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain. FAU - Isoler-Alcaraz, Javier AU - Isoler-Alcaraz J AUID- ORCID: 0000-0002-7400-9679 AD - Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain. FAU - Larriba, Eduardo AU - Larriba E AUID- ORCID: 0000-0001-8838-4974 AD - Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas (CSIC), Madrid 28040, Spain.