ESPE Abstracts (2021) 94 P2-427

1University of Fribourg, Fribourg, Switzerland; 2Centro Andaluz de Biología del Desarrollo, Seville, Spain

Drosophila melanogaster as a study model has already significantly contributed to the understanding of the mechanisms of many human diseases. So far D. melanogaster has rarely been exploited as a model for human sex development. Nanda already demonstrated in 2009 that the Drosophila orthologue of SOX9, Sox100B is essential for testis development in Drosophila. Similarly, we could demonstrate that the fly homolog of STARD8, cv-c, that is suspected to be the cause of sex reversal in two 46 XY sisters, has similar location and function in the fly as its mammalian counterpart. cv-c mutant male flies had defects in formation of embryonic gonads and germ cells (GC) evaiding from their niche. These results indicate that the molecular mechanisms regulating dimorphic gonad development may be much more conserved over phyla than previously suspected. We thus established the fruit fly as a new alternative model to address the general consequences of mutations identified by WES in DSD patients. We use the well-established Gal4-UAS system in flies for high throughput screening for novel DSD causing genes. Firstly, all genes that are known to cause sterility in flies (2576 genes) are predicted with the “DIOPT-DRSC Integrative Ortholog Prediction Tool” to have homologs and/or orthologues in humans (2449 genes) (duplicates are removed). After the already known DSD genes are excluded (126 genes), all other genes then orthologs that are predicted to rank “high” are excluded. The remaining 1265 genes are subsequently knocked down in the germ cells (nos-Gal4) or the somatic gonadal tissue (mtd-Gal4) of the fly. The consequences on sex development will be rated by the female/male ratio of the F1 generation. The obtained fly strains will offer an ideal novel model to study in details the mechanisms underlying sex development and understand its defects.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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