Development, Vol 113, Issue 2 689-699, Copyright © 1991 by Company of Biologists

JOURNAL ARTICLES

Role of c-kit in mouse spermatogenesis: identification of spermatogonia as a specific site of c-kit expression and function

K Yoshinaga, S Nishikawa, M Ogawa, S Hayashi, T Kunisada, T Fujimoto and S Nishikawa
Department of Anatomy, Kumamoto University Medical School, Japan.

Recent studies have shown that the dominant white spotting (W) locus encodes the proto-oncogene c-kit, a member of the tyrosine kinase receptor family. One symptom of mice bearing mutation within this gene is sterility due to developmental failure of the primordial germ cells during early embryogenesis. To elucidate the role of the c-kit in gametogenesis, we used an anti-c-kit monoclonal antibody, ACK2, as an antagonistic blocker for c-kit function to interfere with the development of male and female germ cells during postnatal life. ACK2 enabled us to detect the expression of c-kit in the gonadal tissue and also to determine the functional status of c-kit, which is expressed on the surface of a particular cell lineage. Consistent with our immunohistochemical findings, the intravenous injection of ACK2 into adult mice caused a depletion in the differentiating type A spermatogonia from the testis during 24-36 h, while the undifferentiated type A spermatogonia were basically unaffected. Intraperitoneal injections of ACK2 into prepuberal mice could completely block the mitosis of mature (differentiating) type A spermatogonia, but not the mitosis of the gonocytes and primitive type A spermatogonia, or the meiosis of spermatocytes. Our results indicate that the survival and/or proliferation of the differentiating type A spermatogonia requires c-kit, but the primitive (undifferentiated) type A spermatogonia or spermatogenic stem cells are independent from c-kit. Moreover, the antibody administration had no significant effect on oocyte maturation despite its intense expression of c-kit.
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				M Ogawa, S Nishikawa, K Yoshinaga, S Hayashi, T Kunisada, J Nakao, T Kina, T Sudo, H Kodama, and S Nishikawa Expression and function of c-Kit in fetal hemopoietic progenitor cells: transition from the early c-Kit-independent to the late c-Kit-dependent wave of hemopoiesis in the murine embryo Development, January 3, 1993; 117(3): 1089 - 1098. [Abstract] [PDF]

				C I Brannan, M A Bedell, J L Resnick, J J Eppig, M A Handel, D E Williams, S D Lyman, P J Donovan, N A Jenkins, and N G Copeland Developmental abnormalities in Steel17H mice result from a splicing defect in the steel factor cytoplasmic tail. Genes & Dev., October 1, 1992; 6(10): 1832 - 1842. [Abstract] [PDF]

				L.-X. Feng, N. Ravindranath, and M. Dym Stem Cell Factor/c-kit Up-regulates Cyclin D3 and Promotes Cell Cycle Progression via the Phosphoinositide 3-Kinase/p70 S6 Kinase Pathway in Spermatogonia J. Biol. Chem., August 11, 2000; 275(33): 25572 - 25576. [Abstract] [Full Text] [PDF]

				M. Kanatsu-Shinohara, A. Ogura, M. Ikegawa, K. Inoue, N. Ogonuki, K. Tashiro, S. Toyokuni, T. Honjo, and T. Shinohara Adenovirus-mediated gene delivery and in vitro microinsemination produce offspring from infertile male mice PNAS, February 5, 2002; 99(3): 1383 - 1388. [Abstract] [Full Text] [PDF]