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  • The EMBO Journal (2006) 25, 5816 - 5825
  • doi:10.1038/sj.emboj.7601447

Published online: 23 November 2006

Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells

Nadège Vernet1, Christine Dennefeld1, Florian Guillou2, Pierre Chambon1, Norbert B Ghyselinck1 and Manuel Mark1

  1. IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM, U596, Illkirch, France; CNRS, UMR7104, Illkirch, France; Faculté de Médecine, Strasbourg, France
  2. INRA, Université de Tours, Nouzilly, France

Correspondence to:

Norbert B Ghyselinck, IGBMC, 1 rue Laurent Fries, BP10142, Illkirch F-67404, France. Tel.: +33 388 655 674; Fax: +33 388 653 201; E-mail: norbert@igbmc.u-strasbg.fr

Manuel Mark, IGBMC, 1 rue Laurent Fries, BP10142, Illkirch F-67404, France. Tel.: +33 388 655 636; Fax: +33 388 653 201; E-mail: marek@igbmc.u-strasbg.fr

Received 21 August 2006; Accepted 24 October 2006

Sertoli cells (SC) are instrumental to stem spermatogonia differentiation, a process that critically depends on retinoic acid (RA). We show here that selective ablation of RA receptor alpha (RARalpha) gene in mouse SC, singly (RaraSer-/- mutation) or in combination with RARbeta and RARgamma genes (Rara/b/gSer-/- mutation), abolishes cyclical gene expression in these cells. It additionally induces testis degeneration and delays spermatogonial expression of Stra8, two hallmarks of RA deficiency. As identical defects are generated upon inactivation of RARalpha in the whole organism, our data demonstrate that all the functions exerted by RARalpha in male reproduction are Sertoli cell-autonomous. They further indicate that RARalpha is a master regulator of the cyclical activity of SC and controls paracrine pathways required for spermatogonia differentiation and germ cell survival. Most importantly, we show that the ablation of all RXR (alpha, beta and gamma isotypes) in SC does not recapitulate the phenotype generated upon ablation of all three RARs, thereby providing the first evidence that RARs exert functions in vivo independently of RXRs.

  • Keywords:

    • biological rhythms,
    • germ cells,
    • heterodimers,
    • nuclear receptors,
    • spermatogenesis