Role of c-kit in mammalian spermatogenesis.
The tyrosine-kinase receptor c-kit and its ligand, stem cell factor (SCF), are essential for the maintenance of primordial germ cells (PGCs) in both sexes. However, c-kit and a post-meiotic-specific alternative c-kit gene product play important roles also during post-natal stages of spermatogenesis. In the adult testis, the c-kit receptor is re-expressed in differentiating spermatogonia, but not in spermatogonial stem cells, whereas SCF is expressed by Sertoli cells under FSH stimulation. SCF stimulates DNA synthesis in type A spermatogonia cultured in vitro, and injection of anti-c-kit antibodies blocks their proliferation in vivo. A point mutation in the c-kit gene, which impairs SCF-mediated activation of phosphatidylinositol 3-kinase, does not cause any significant reduction in PGCs number during embryonic development, nor in spermatogonial stem cell populations. However males are completely sterile due to a block in the initial stages of spermatogenesis, associated to abolishment of DNA-synthesis in differentiating A1-A4 spermatogonia. With the onset of meiosis c-kit expression ceases, but a truncated c-kit product, tr-kit, is specifically expressed in post-meiotic stages of spermatogenesis, and is accumulated in mature spermatozoa. Microinjection of tr-kit into mouse eggs causes their parthenogenetic activation, suggesting that it might play a role in the final function of the gametes, fertilization.
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Dipartimento di Sanità Pubblica e Biologia Cellulare, Università Tor Vergata, Roma, Italy. pellegrino.rossi@med.uniroma2.it
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D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D005306:Fertilization; D006801:Humans; D008297:Male; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology*; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology; D019089:Stem Cell Factor / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000254:growth & development
D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit