Gametogenesis (spermatogenesis and oogenesis) includes mitotic expansion of stem cells, meiotic recombination of genetic information, and execution of dedicated gene expression programs. We study molecular and cellular factors implicated in control of gametogenesis. In collaboration with the Erasmus MC Departments of Cell Biology, Genetics, and Clinical Cenetics (Jan Hoeijmakers, Roland Kanaar, Sjaak Philipsen, Niels Galjart, Ben Oostra, et al.), we develop and investigate transgenic (knockout and knock-in) mouse models to study different aspects of male and female gametogenesis and development. In this research, we apply live cellular imaging technology to obtain insight in the molecular dynamics of meiotic recombination and chromatin remodeling during the meiotic prophase. To facilitate transfer of knowledge to the clinic, the focus is on genes and proteins that are conserved between mouse and human. Also, we study gametogenic chromatin rearrangements and genome instability, in relation to early embryonic development, since we feel that this is highly relevant in relation to evaluation of possible risk factors associated with clinical application of assisted reproduction techniques. The hedgehog family of secreted signaling proteins regulates tissue growth and patterning during embryonic development and is also involved in tissue maintenance in the adult. In mammalian species, this family includes three members: Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). Dysregulation of testis development in Dhh knockout mice provided an indication for a possible role of hedgehog signaling in mammalian gonads. Currently we are investigating the activity of the hedgehog signalling pathway during gonadal development and in different human pathological tissue samples. The results provide evidence that both Ihh and Dhh act as paracrine factors in the interactions between the different somatic cell compartments within the gonads, implying a more prominent role for hedgehog signaling in steroidogenesis rather than gametogenesis.