Norbert GhyselinckThe goal of my research is to understand the function of all-trans retinoic acid (ATRA) receptors (RARs) during development and in germ cell physiology. Early in my career I gained a background in reproductive biology with expertise in the are of nuclear receptor signaling. This inspired my research direction. As a postdoctoral fellow in the group of Pr Pierre CHAMBON, I generated and analyzed mutant mice lacking the beta isotype of RAR. Obtaining a permanent position of researcher at the French CNRS (Centre National de la Recherche Scientifique) in 1998, my research led to the characterization of a large panel of RAR-deprived mutant models, yielding the first evidence that (i) RXR/RAR heterodimers are transducers of the ATRA signal in vivo, (ii) specific heterodimers are required at many distinct stages during early embryogenesis and organogenesis, (iii) the physiological role of ATRA and its nuclear receptors cannot be extrapolated from teratogenesis studies using retinoids in excess. In 2001, I founded my own research team at Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC), and expanded my research into the function of ATRA synthesizing enzymes during development. Later, by studying spatiotemporally loss-of-function genetic mouse models, I investigated the role of RARs in gametogenesis. As a PI on several ANR-funded grants, I showed that ATRA-activated RARs acting both in spermatogonia and in supporting, Sertoli, cells of the seminiferous epithelium are necessary to induce spermatogonia differentiation. I also provided genetic evidence that RARs (as well as ATRA-synthesizing enzymes) are fully dispensable for meiotic initiation in both oocytes and spermatocytes, disqualifying thereby ATRA act as the long-searched meiosis-inducing substance. I was an author on several reviews including a 2006 article in Annual Reviews in Pharmacology and Toxicology summarizing the function of RAR during mouse embryogenesis and organogenesis. In 2015 and 2017, my laboratory published two reviews in Biochimica et Biophysica Acta and in Current Topics in Developmental Biology summarizing the knowledge on the function of ATRA-activated RARs in germ cell differentiation gained by studying loss-of-function mouse models. In 2019, I published a Development at A Glance review on ATRA signaling in Development along with Pr. Duester who is a co-Editor in this volume of Current Topics in Developmental Biology. As Pr. Duester, my goal now is to bring knowledge of how ATRA normally functions to as wide an audience as possible. Read More Read Less