Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1991 Sep;10(9):2425–2435. doi: 10.1002/j.1460-2075.1991.tb07782.x

Embryonic RNA expression patterns of the c-kit receptor and its cognate ligand suggest multiple functional roles in mouse development.

E Keshet 1, S D Lyman 1, D E Williams 1, D M Anderson 1, N A Jenkins 1, N G Copeland 1, L F Parada 1
PMCID: PMC452938  PMID: 1714375

Abstract

Mutations at the dominant white spotting (W) and Steel (Sl) loci in mouse exert deleterious effects on three migratory cell lineages (primordial germ cells, melanocytes and hematopoietic stem cells) resulting in loss of pigmentation, reduced fertility and anemia. The W locus encodes the c-kit protein tyrosine kinase (TK) receptor. More recently, the Sl locus has been shown to encode a ligand for c-kit, which is variously known as mast cell growth factor (MGF), stem cell growth factor and c-kit ligand. Here we report an in situ hybridization analysis comparing the expression profiles of MGF and c-kit transcripts during mouse embryogenesis. The data are consistent with the c-kit receptor-ligand complex providing a homing mechanism during stem cell migration in early development and in stem cell proliferation, differentiation, or survival in late development. In the nervous system, an unexpected and complex pattern of expression is uncovered that suggests involvement of the W and Sl gene products in the organization of the neural tube and brain.

Full text

PDF
2425

Images in this article

2426Image
on p.2426
2427Image
on p.2427
2428Image
on p.2428
2429Image
on p.2429
2430Image
on p.2430
2431Image
on p.2431
2432Image
on p.2432
2433Image
on p.2433

Selected References

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

  1. Altus M. S., Bernstein S. E., Russell E. S., Carsten A. L., Upton A. C. Defect extrinsic to stem cells in spleens of steel anemic mice. Proc Soc Exp Biol Med. 1971 Dec;138(3):985–988. doi: 10.3181/00379727-138-36032. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Basler K., Hafen E. Sevenless and Drosophila eye development: a tyrosine kinase controls cell fate. Trends Genet. 1988 Mar;4(3):74–79. doi: 10.1016/0168-9525(88)90044-3. [DOI] [PubMed] [Google Scholar]
  4. Beechey C. V., Searle A. G. Contrasted, a steel allele in the mouse with intermediate effects. Genet Res. 1983 Oct;42(2):183–191. doi: 10.1017/s0016672300021649. [DOI] [PubMed] [Google Scholar]
  5. Boswell H. S., Mochizuki D. Y., Burgess G. S., Gillis S., Walker E. B., Anderson D., Williams D. E. A novel mast cell growth factor (MCGF-3) produced by marrow-adherent cells that synergizes with interleukin 3 and interleukin 4. Exp Hematol. 1990 Aug;18(7):794–800. [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Dodd J., Jessell T. M. Axon guidance and the patterning of neuronal projections in vertebrates. Science. 1988 Nov 4;242(4879):692–699. doi: 10.1126/science.3055291. [DOI] [PubMed] [Google Scholar]
  9. Donovan P. J., Stott D., Cairns L. A., Heasman J., Wylie C. C. Migratory and postmigratory mouse primordial germ cells behave differently in culture. Cell. 1986 Mar 28;44(6):831–838. doi: 10.1016/0092-8674(86)90005-x. [DOI] [PubMed] [Google Scholar]
  10. Fried W., Chamberlin W., Knospe W. H., Husseini S., Trobaugh F. E., Jr Studies on the defective haematopoietic microenvironment of Sl/Sl d mice. Br J Haematol. 1973 May;24(5):643–650. doi: 10.1111/j.1365-2141.1973.tb01690.x. [DOI] [PubMed] [Google Scholar]
  11. Geissler E. N., McFarland E. C., Russell E. S. Analysis of pleiotropism at the dominant white-spotting (W) locus of the house mouse: a description of ten new W alleles. Genetics. 1981 Feb;97(2):337–361. doi: 10.1093/genetics/97.2.337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
  14. Harrison D. E., Russell E. S. The response of W-W v and Sl-Sl d anaemic mice to haemopoietic stimuli. Br J Haematol. 1972 Feb;22(2):155–168. doi: 10.1111/j.1365-2141.1972.tb08797.x. [DOI] [PubMed] [Google Scholar]
  15. Hempstead B. L., Martin-Zanca D., Kaplan D. R., Parada L. F., Chao M. V. High-affinity NGF binding requires coexpression of the trk proto-oncogene and the low-affinity NGF receptor. Nature. 1991 Apr 25;350(6320):678–683. doi: 10.1038/350678a0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Joyner A. L., Herrup K., Auerbach B. A., Davis C. A., Rossant J. Subtle cerebellar phenotype in mice homozygous for a targeted deletion of the En-2 homeobox. Science. 1991 Mar 8;251(4998):1239–1243. doi: 10.1126/science.1672471. [DOI] [PubMed] [Google Scholar]
  18. Kaplan D. R., Hempstead B. L., Martin-Zanca D., Chao M. V., Parada L. F. The trk proto-oncogene product: a signal transducing receptor for nerve growth factor. Science. 1991 Apr 26;252(5005):554–558. doi: 10.1126/science.1850549. [DOI] [PubMed] [Google Scholar]
  19. Kaplan D. R., Martin-Zanca D., Parada L. F. Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature. 1991 Mar 14;350(6314):158–160. doi: 10.1038/350158a0. [DOI] [PubMed] [Google Scholar]
  20. Kitamura Y., Go S. Decreased production of mast cells in S1/S1d anemic mice. Blood. 1979 Mar;53(3):492–497. [PubMed] [Google Scholar]
  21. Klein R., Martin-Zanca D., Barbacid M., Parada L. F. Expression of the tyrosine kinase receptor gene trkB is confined to the murine embryonic and adult nervous system. Development. 1990 Aug;109(4):845–850. doi: 10.1242/dev.109.4.845. [DOI] [PubMed] [Google Scholar]
  22. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  23. MCCULLOCH E. A., SIMINOVITCH L., TILL J. E. SPLEEN-COLONY FORMATION IN ANEMIC MICE OF GENOTYPE WW. Science. 1964 May 15;144(3620):844–846. doi: 10.1126/science.144.3620.844. [DOI] [PubMed] [Google Scholar]
  24. MINTZ B., RUSSELL E. S. Gene-induced embryological modifications of primordial germ cells in the mouse. J Exp Zool. 1957 Mar;134(2):207–237. doi: 10.1002/jez.1401340202. [DOI] [PubMed] [Google Scholar]
  25. Martin-Zanca D., Barbacid M., Parada L. F. Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development. Genes Dev. 1990 May;4(5):683–694. doi: 10.1101/gad.4.5.683. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. 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]
  28. Mayer T. C., Green M. C. An experimental analysis of the pigment defect caused by mutations at the W and S1 loci in mice. Dev Biol. 1968 Jul;18(1):62–75. doi: 10.1016/0012-1606(68)90023-7. [DOI] [PubMed] [Google Scholar]
  29. McCoshen J. A., McCallion D. J. A study of the primordial germ cells during their migratory phase in Steel mutant mice. Experientia. 1975 May 15;31(5):589–590. doi: 10.1007/BF01932475. [DOI] [PubMed] [Google Scholar]
  30. Morrison-Graham K., West-Johnsrud L., Weston J. A. Extracellular matrix from normal but not Steel mutant mice enhances melanogenesis in cultured mouse neural crest cells. Dev Biol. 1990 Jun;139(2):299–307. doi: 10.1016/0012-1606(90)90299-x. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Placzek M., Tessier-Lavigne M., Jessell T., Dodd J. Orientation of commissural axons in vitro in response to a floor plate-derived chemoattractant. Development. 1990 Sep;110(1):19–30. doi: 10.1242/dev.110.1.19. [DOI] [PubMed] [Google Scholar]
  33. Rettenmier C. W. Biosynthesis of macrophage colony-stimulating factor (CSF-1): differential processing of CSF-1 precursors suggests alternative mechanisms for stimulating CSF-1 receptors. Curr Top Microbiol Immunol. 1989;149:129–141. doi: 10.1007/978-3-642-74623-9_12. [DOI] [PubMed] [Google Scholar]
  34. Russell E. S., Bernstein S. E. Proof of whole-cell implant in therapy of W-series anemia. Arch Biochem Biophys. 1968 May;125(2):594–597. doi: 10.1016/0003-9861(68)90617-6. [DOI] [PubMed] [Google Scholar]
  35. Russell E. S. Hereditary anemias of the mouse: a review for geneticists. Adv Genet. 1979;20:357–459. [PubMed] [Google Scholar]
  36. Tessier-Lavigne M., Placzek M., Lumsden A. G., Dodd J., Jessell T. M. Chemotropic guidance of developing axons in the mammalian central nervous system. Nature. 1988 Dec 22;336(6201):775–778. doi: 10.1038/336775a0. [DOI] [PubMed] [Google Scholar]
  37. Turner D. L., Cepko C. L. A common progenitor for neurons and glia persists in rat retina late in development. Nature. 1987 Jul 9;328(6126):131–136. doi: 10.1038/328131a0. [DOI] [PubMed] [Google Scholar]
  38. Williams D. E., Eisenman J., Baird A., Rauch C., Van Ness K., March C. J., Park L. S., Martin U., Mochizuki D. Y., Boswell H. S. Identification of a ligand for the c-kit proto-oncogene. Cell. 1990 Oct 5;63(1):167–174. doi: 10.1016/0092-8674(90)90297-r. [DOI] [PubMed] [Google Scholar]
  39. 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]

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

RESOURCES