Project at a glance

Sex determination and testis development

Our long-standing interest lies in the elucidation of the molecular mechanisms regulating gonadal differentiation and testicular function. More precisely, we are investigating the following topics.

1. The role of insulin signaling in regulating sex determination and testicular function

The insulin family of growth factor including insulin, Igf1 and Igf2 is essential for male reproductive function and spermatogenesis. Studying the function of these growth factors by constitutive invalidation of their cognate receptor is difficult due to perinatal lethality. We are currently developing a line of research aimed at identifying the function of the insulin signaling in each relevant cell lineage of the testis using the Cre/lox technology. So far, our results suggest that both Insr and Igf1r are essential for proper testicular and ovarian differentiation, adrenal specification, testis size and steroidogenesis.

2. Roles of microRNAs in testicular development and function

Recently, a novel mechanism of post transcriptional regulation mediated by microRNAs has emerged. MicroRNAs are non-protein-coding small RNAs that act by negatively regulating gene expression at the post-transcriptional level either by degrading target mRNA or by inhibiting translation. Specific lines of genetically modified mice provide platforms to study aspects of testicular differentiation and function. Our data provide in vivo evidence that Dicer, a RNAseIII-related enzyme responsible for processing miRNAs to the mature form, and by inference miRNAs are essential for normal spermatogenesis. Specific ablation of Dicer, either in the germ cell lineage or in Sertoli cells, leads to infertility due to the incapacity of mutant mouse testes to complete spermatogenesis. We are in the process of identifying which miRNAs expressed in Sertoli cells and/or germ cells are important for spermatogenesis and what are their relevant target genes.