Skip to main content
PMC home page
The EMBO Journal logoLink to The EMBO Journal
. 1991 Aug;10(8):2111–2118. doi: 10.1002/j.1460-2075.1991.tb07744.x

In utero manipulation of coat color formation by a monoclonal anti-c-kit antibody: two distinct waves of c-kit-dependency during melanocyte development.

S Nishikawa 1, M Kusakabe 1, K Yoshinaga 1, M Ogawa 1, S Hayashi 1, T Kunisada 1, T Era 1, T Sakakura 1, S Nishikawa 1
PMCID: PMC452897  PMID: 1712289

Abstract

Previous studies on mice bearing various mutations within the c-kit gene, dominant white spotting (W), indicate the functional role of this tyrosine kinase receptor in the development of melanocytes, germ cells and hematopoietic cells. Despite the availability of mice defective in the c-kit gene and a respectable understanding of the molecular nature of c-kit, however, it is not clear at what stage of gestation c-kit is functionally required for the development of each of these cell lineages. To address this question, we have used a monoclonal anti-c-kit antibody, ACK2, as an antagonistic blocker of c-kit function to interfere with the development of melanocytes during embryonic and postnatal life. ACK2 injected intradermally into pregnant mice entered the embryos where it blocked the proper development of melanocytes. This inhibitory effect was manifested as coat color alteration in the offspring. Furthermore, ACK2 injection also altered the coat color of neonatal and adult mice. Based on the coat color patterns produced by ACK2 administration at various stages before or after birth, the following conclusions are drawn: (i) during mid-gestation, c-kit is functionally required during a restricted period around day 14.5 post-coitum when a sequence of events leading to melanocyte entry into the epidermal layer occurs; (ii) during postnatal life, c-kit is required for melanocyte activation which occurs concomitantly with the hair cycle which continues throughout life after neonatal development of the first hair.

Full text

PDF

Images in this article

2112Image
on p.2112
2113Image
on p.2113
2114Image
on p.2114
2115Image
on p.2115
2116Image
on p.2116
2116Image
on p.2116
2117Image
on p.2117

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. M., Lyman S. D., Baird A., Wignall J. M., Eisenman J., Rauch C., March C. J., Boswell H. S., Gimpel S. D., Cosman D. Molecular cloning of mast cell growth factor, a hematopoietin that is active in both membrane bound and soluble forms. Cell. 1990 Oct 5;63(1):235–243. doi: 10.1016/0092-8674(90)90304-w. [DOI] [PubMed] [Google Scholar]
  2. Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Besmer P., Murphy J. E., George P. C., Qiu F. H., Bergold P. J., Lederman L., Snyder H. W., Jr, Brodeur D., Zuckerman E. E., Hardy W. D. A new acute transforming feline retrovirus and relationship of its oncogene v-kit with the protein kinase gene family. Nature. 1986 Apr 3;320(6061):415–421. doi: 10.1038/320415a0. [DOI] [PubMed] [Google Scholar]
  4. Chabot B., Stephenson D. A., Chapman V. M., Besmer P., Bernstein A. The proto-oncogene c-kit encoding a transmembrane tyrosine kinase receptor maps to the mouse W locus. Nature. 1988 Sep 1;335(6185):88–89. doi: 10.1038/335088a0. [DOI] [PubMed] [Google Scholar]
  5. Copeland N. G., Gilbert D. J., Cho B. C., Donovan P. J., Jenkins N. A., Cosman D., Anderson D., Lyman S. D., Williams D. E. Mast cell growth factor maps near the steel locus on mouse chromosome 10 and is deleted in a number of steel alleles. Cell. 1990 Oct 5;63(1):175–183. doi: 10.1016/0092-8674(90)90298-s. [DOI] [PubMed] [Google Scholar]
  6. Dexter T. M., Allen T. D., Lajtha L. G. Conditions controlling the proliferation of haemopoietic stem cells in vitro. J Cell Physiol. 1977 Jun;91(3):335–344. doi: 10.1002/jcp.1040910303. [DOI] [PubMed] [Google Scholar]
  7. Geissler E. N., Ryan M. A., Housman D. E. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988 Oct 7;55(1):185–192. doi: 10.1016/0092-8674(88)90020-7. [DOI] [PubMed] [Google Scholar]
  8. Hattori M., Sudo T., Iizuka M., Kobayashi S., Nishio S., Kano S., Minato N. Generation of continuous large granular lymphocyte lines by interleukin 2 from the spleen cells of mice infected with Moloney leukemia virus. Involvement of interleukin 3. J Exp Med. 1987 Oct 1;166(4):833–849. doi: 10.1084/jem.166.4.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hayashi S., Kunisada T., Ogawa M., Yamaguchi K., Nishikawa S. Exon skipping by mutation of an authentic splice site of c-kit gene in W/W mouse. Nucleic Acids Res. 1991 Mar 25;19(6):1267–1271. doi: 10.1093/nar/19.6.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Huang E., Nocka K., Beier D. R., Chu T. Y., Buck J., Lahm H. W., Wellner D., Leder P., Besmer P. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell. 1990 Oct 5;63(1):225–233. doi: 10.1016/0092-8674(90)90303-v. [DOI] [PubMed] [Google Scholar]
  11. Kimoto M., Kishimoto S. Alteration of the T cell self-specificity repertoire by treatment with anti-Ia antibody during embryonic life. Eur J Immunol. 1986 Jul;16(7):835–839. doi: 10.1002/eji.1830160719. [DOI] [PubMed] [Google Scholar]
  12. Kitamura Y., Go S. Decreased production of mast cells in S1/S1d anemic mice. Blood. 1979 Mar;53(3):492–497. [PubMed] [Google Scholar]
  13. Matsui Y., Zsebo K. M., Hogan B. L. Embryonic expression of a haematopoietic growth factor encoded by the Sl locus and the ligand for c-kit. Nature. 1990 Oct 18;347(6294):667–669. doi: 10.1038/347667a0. [DOI] [PubMed] [Google Scholar]
  14. Mayer T. C. A comparison of pigment cell development in albino, steel, and dominant-spotting mutant mouse embryos. Dev Biol. 1970 Oct;23(2):297–309. doi: 10.1016/0012-1606(70)90100-4. [DOI] [PubMed] [Google Scholar]
  15. Nakano T., Sonoda T., Hayashi C., Yamatodani A., Kanayama Y., Yamamura T., Asai H., Yonezawa T., Kitamura Y., Galli S. J. Fate of bone marrow-derived cultured mast cells after intracutaneous, intraperitoneal, and intravenous transfer into genetically mast cell-deficient W/Wv mice. Evidence that cultured mast cells can give rise to both connective tissue type and mucosal mast cells. J Exp Med. 1985 Sep 1;162(3):1025–1043. doi: 10.1084/jem.162.3.1025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nakayama H., Kuroda H., Fujita J., Kitamura Y. Studies of Sl/Sld in equilibrium with +/+ mouse aggregation chimaeras. I. Different distribution patterns between melanocytes and mast cells in the skin. Development. 1988 Jan;102(1):107–116. doi: 10.1242/dev.102.1.107. [DOI] [PubMed] [Google Scholar]
  17. Nishikawa S., Ogawa M., Nishikawa S., Kunisada T., Kodama H. B lymphopoiesis on stromal cell clone: stromal cell clones acting on different stages of B cell differentiation. Eur J Immunol. 1988 Nov;18(11):1767–1771. doi: 10.1002/eji.1830181117. [DOI] [PubMed] [Google Scholar]
  18. Nishikawa S., Sasaki Y., Kina T., Amagai T., Katsura Y. A monoclonal antibody against Igh6-4 determinant. Immunogenetics. 1986;23(2):137–139. doi: 10.1007/BF00377976. [DOI] [PubMed] [Google Scholar]
  19. Nocka K., Tan J. C., Chiu E., Chu T. Y., Ray P., Traktman P., Besmer P. Molecular bases of dominant negative and loss of function mutations at the murine c-kit/white spotting locus: W37, Wv, W41 and W. EMBO J. 1990 Jun;9(6):1805–1813. doi: 10.1002/j.1460-2075.1990.tb08305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Orr-Urtreger A., Avivi A., Zimmer Y., Givol D., Yarden Y., Lonai P. Developmental expression of c-kit, a proto-oncogene encoded by the W locus. Development. 1990 Aug;109(4):911–923. doi: 10.1242/dev.109.4.911. [DOI] [PubMed] [Google Scholar]
  21. Qiu F. H., Ray P., Brown K., Barker P. E., Jhanwar S., Ruddle F. H., Besmer P. Primary structure of c-kit: relationship with the CSF-1/PDGF receptor kinase family--oncogenic activation of v-kit involves deletion of extracellular domain and C terminus. EMBO J. 1988 Apr;7(4):1003–1011. doi: 10.1002/j.1460-2075.1988.tb02907.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Raghupathy R., Singh B., Leigh J. B., Wegmann T. G. The ontogeny and turnover kinetics of paternal H-2K antigenic determinants on the allogeneic murine placenta. J Immunol. 1981 Nov;127(5):2074–2079. [PubMed] [Google Scholar]
  23. Russell E. S. Hereditary anemias of the mouse: a review for geneticists. Adv Genet. 1979;20:357–459. [PubMed] [Google Scholar]
  24. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  25. Yarden Y., Kuang W. J., Yang-Feng T., Coussens L., Munemitsu S., Dull T. J., Chen E., Schlessinger J., Francke U., Ullrich A. Human proto-oncogene c-kit: a new cell surface receptor tyrosine kinase for an unidentified ligand. EMBO J. 1987 Nov;6(11):3341–3351. doi: 10.1002/j.1460-2075.1987.tb02655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Zsebo K. M., Williams D. A., Geissler E. N., Broudy V. C., Martin F. H., Atkins H. L., Hsu R. Y., Birkett N. C., Okino K. H., Murdock D. C. Stem cell factor is encoded at the Sl locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor. Cell. 1990 Oct 5;63(1):213–224. doi: 10.1016/0092-8674(90)90302-u. [DOI] [PubMed] [Google Scholar]
  27. Zuñiga-Pflücker J. C., McCarthy S. A., Weston M., Longo D. L., Singer A., Kruisbeek A. M. Role of CD4 in thymocyte selection and maturation. J Exp Med. 1989 Jun 1;169(6):2085–2096. doi: 10.1084/jem.169.6.2085. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES