Melanocyte Precursors in Patch Mutant Embryos
473Pigment Defect in the Ph Mutation
C. W. (1995). Lethality of Rw/Rw mouse embryos during early pathway. This competition results from ectopic expression
postimplantation development. Dev. Biol. 168, 307– 318.
of c-kit by dermal mesenchyme, possibly caused by the
re-Conlon, R. A., and Rossant, J. (1992). Exogenous retinoic acid rap-moval of c-kit regulatory elements by the Patch genomic
idly induces anterior ectopic expression of murine Hox-2 genes deletion. This inference is supported by the phenotype of
in vivo. Development 116, 357 –368.
mice carrying a targeted mutation in the PDGFRa gene,
Copeland, N., Gilbert, D., Cho, B., Donovan, P., Jenkins, N., Cos-which, unlike the Patch deletion, do not exhibit a pigmenta- man, D., Anderson, D., Lyman, S., and Williams, D. (1990). Mast tion phenotype as heterozygotes (P. Soriano, personal com- cell growth factor maps near the Steel locus on mouse chromo-munication). This result suggests that the Patch mutation some 10 and is deleted in a number of Steel allels. Cell 63, 175–
acts non-cell-autonomously to affect the development of 183.
Copeland, N. G., Gilbert, D. J., Jenkins, N. A., Nadeau, J. H., Eppig, MPs and further emphasizes the importance of
characteriz-J. T., Maltais, L. characteriz-J., Miller, characteriz-J. C., Dietrich, W. F., Steen, R. G., ing the role of c-kit regulatory elements for c-kit expression
Lincoln, S. E., Weaver, A., Joyce, D. C., Merchant, M., Wessel, in vivo.
M., Katz, H., Stein, L. D., Reeve, M. P., Daly, M. J., Dredge, R. D., Marquis, A., Goodman, N., and Lander, E. S. (1993).
Genome map IV. Science 262, 67– 82.
ACKNOWLEDGMENTS
Dietrich, W. F., Miller, J. C., Steen, R. G., Merchant, M., Damron, D., Nahf, R., Gross, A., Joyce, D. C., Wessel, M., Dredge, R. D., We thank Sheree Harrison for excellent technical assistance. We Marquis, A., Stein, L., Goodman, N., Page, D. C., and Lander, are grateful to Monique Wehrle-Haller and Dr. Stephen Johnson E. S. (1994). A genetic map of the mouse with 4006 simple se-for their critical comments on the manuscript. We also thank Drs. quence lenght polymorphisms. Nature Genet. 7, 220 –245.John Flanagan, Ian Jackson, Robert Arceci, and Dan Bowen-Pope Duttlinger, R., Manova, K., Chu, T. Y., Gyssler, C., Zelenetz, for generously providing cDNA plasmids and Dr. Peter Lonai for A. D., Bachvarova, R. F., and Besmer, P. (1993). W-sash affects sharing primer sequences. We thank Drs. Shin-Ichi Nishikawa and positive and negative elements controlling c-kit expression: Ec-Douglas Williams for generously providing ACK-2 anti-c-kit rat topic c-kit expression at sites of kit-ligand expression affects mel-monoclonal antibody and recombinant SlF and antiserum to SlF, anogenesis. Development 118, 707–717.
respectively. Special thanks to Drs. Deborah Nagle, Maja Bucan, Duttlinger, R., Manova, K., Berrozpe, G., Chu, T.-Y., DeLeon, V., and Peter Besmer for technical advice, discussions, and for sharing Timokhina, I., Chaganti, R. S. K., Zelenetz, A. D., Bachvarova, results in press, Phillipe Soriano for sharing unpublished results, R. F., and Besmer, P. (1995). The Wshand Ph mutations affect the and Yoshiko Takahashi and Yoshio Wakamatsu for advice on in c-kit expression profile: c-kit misexpression in embryogenesis situand whole mount immunohistochemistry. Drs. Sherry Rogers impairs melanogenesis in Wshand Ph mutant mice. Proc. Natl.
and Carol Erickson provided helpful advice and criticisms. We are Acad. Sci. USA92, 3754–3758.
especially grateful to Rick Gosswiler for his careful animal hus- Erickson, C. A., and Weston, J. A. (1983). An SEM analysis of neural bandry and to Tom Maynard for advice concerning computer im- crest migration in the mouse. J. Embryol. Exp. Morphol. 74, 97–
aging methods. Our work has been supported by Grant DE-04316 118.
from the USPHS. B.W.-H. has been supported by an EMBO postdoc- Evans, G. I., Lewis, G. K., Ramsay, G., and Bishop, J. M. (1985).
toral fellowship (169-1993) and a grant from the Swiss Foundation Isolation of monoclonal antibodies specific for human c-myc for Medical and Biological Fellowships. proto-oncogene product. Mol. Cell. Biol. 5, 3610– 3616.
Flanagan, J., Chan, D., and Leder, P. (1991). Transmembrane form of the kit ligand growth factor is determined by alternative splic-ing and is misssplic-ing in the Sldmutant. Cell 64, 1025– 1035.
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Received for publication December 23, 1995 receptora-subunit expression during embryogenesis.
Develop-ment115, 123– 131. Accepted February 12, 1996
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2.4. Stem Cell factor dependent migration and/or survival ?
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2.5. Stem Cell factor induces chemotactic migration of melanocytes
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