CREM: a master-switch governing male germ cells differentiation and apoptosis.
Several endocrine and neuronal functions are governed by the cAMP-dependent signalling pathway. In eukaryotes, transcriptional regulation upon stimulation of the adenylyl cyclase signalling pathway is mediated by a family of cAMP-responsive nuclear factors. The CREM gene plays a key physiological and developmental role within the hypothalamic-pituitary-gonadal axis. CREM is highly expressed in postmeiotic cells upon a striking developmental switch regulated by the pituitary hormone FSH. CREM-mutant mice generated by homologous recombination reveal that spermatogenesis stops at the first step of spermiogenesis. Late spermatids are completely absent while there is a significant increase in apoptotic germ cells. A series of post-meiotic germ cell-specific genes are not expressed. Mutant male mice completely lack spermatozoa. This phenotype is reminiscent of cases of human infertility.
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Institut de Génétique et de Biologie Mole@a3culaire et Cellulaire, Centre National de la Recherche Scientifique INSERM-ULP, 67404 Illkirch, Strasbourg, France.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D051786:Cyclic AMP Response Element Modulator; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D012097:Repressor Proteins / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator