Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1993 May 1;121(3):631–641. doi: 10.1083/jcb.121.3.631

Mouse notch: expression in hair follicles correlates with cell fate determination

PMCID: PMC2119559  PMID: 8486742

Abstract

Many vertebrate tissues, including skin, are known to develop as a consequence of epithelial-mesenchymal interactions. Much less is known about the role of cell-cell interaction within the epithelial or the mesenchymal compartments in morphogenesis. To investigate cell-cell interactions during skin development, and the potential role of the Notch homolog in this process, we cloned the mouse homolog of Notch (mNotch) and studied its expression pattern, starting as early as mesoderm formation. The novel application of double-labeled in situ hybridization in vertebrates allowed high resolution analysis to follow the fate of mNotch expressing cells directly. In comparison with the distribution of Id mRNA, analysis confirmed that in the hair follicle high levels of mNotch are expressed exclusively in the epithelial compartment. Hair follicle matrix cells start expressing mNotch as different cell types become distinguishable in the developing follicle. mNotch mRNA expression persists throughout the growth phase of the follicle and maintains the same expression profile in the second hair cycle. The cells in the follicle that undergo a phase of high level mNotch expression are in transition from mitotic precursors to several discreet, differentiating cell types. Our observations point out that both in time (during development) and in space (by being removed one cell layer from the dermal papilla) mNotch expression is clearly separated from the inductive interactions. This is a novel finding and suggests that mNotch is important for follicular differentiation and possibly cell fate selection within the follicle.

Full Text

The Full Text of this article is available as a PDF (7.5 MB).

Selected References

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

  1. Adams M. D., Kelley J. M., Gocayne J. D., Dubnick M., Polymeropoulos M. H., Xiao H., Merril C. R., Wu A., Olde B., Moreno R. F. Complementary DNA sequencing: expressed sequence tags and human genome project. Science. 1991 Jun 21;252(5013):1651–1656. doi: 10.1126/science.2047873. [DOI] [PubMed] [Google Scholar]
  2. Artavanis-Tsakonas S., Simpson P. Choosing a cell fate: a view from the Notch locus. Trends Genet. 1991 Nov-Dec;7(11-12):403–408. doi: 10.1016/0168-9525(91)90264-q. [DOI] [PubMed] [Google Scholar]
  3. Benezra R., Davis R. L., Lockshon D., Turner D. L., Weintraub H. The protein Id: a negative regulator of helix-loop-helix DNA binding proteins. Cell. 1990 Apr 6;61(1):49–59. doi: 10.1016/0092-8674(90)90214-y. [DOI] [PubMed] [Google Scholar]
  4. Bertolino A. P., Checkla D. M., Heitner S., Freedberg I. M., Yu D. W. Differential expression of type I hair keratins. J Invest Dermatol. 1990 Mar;94(3):297–303. doi: 10.1111/1523-1747.ep12874436. [DOI] [PubMed] [Google Scholar]
  5. Cagan R. L., Ready D. F. Notch is required for successive cell decisions in the developing Drosophila retina. Genes Dev. 1989 Aug;3(8):1099–1112. doi: 10.1101/gad.3.8.1099. [DOI] [PubMed] [Google Scholar]
  6. Coffman C., Harris W., Kintner C. Xotch, the Xenopus homolog of Drosophila notch. Science. 1990 Sep 21;249(4975):1438–1441. doi: 10.1126/science.2402639. [DOI] [PubMed] [Google Scholar]
  7. Cotsarelis G., Sun T. T., Lavker R. M. Label-retaining cells reside in the bulge area of pilosebaceous unit: implications for follicular stem cells, hair cycle, and skin carcinogenesis. Cell. 1990 Jun 29;61(7):1329–1337. doi: 10.1016/0092-8674(90)90696-c. [DOI] [PubMed] [Google Scholar]
  8. Davidson D. The mechanism of feather pattern development in the chick. 1. The time of determination of feather position. J Embryol Exp Morphol. 1983 Apr;74:245–259. [PubMed] [Google Scholar]
  9. Del Amo F. F., Smith D. E., Swiatek P. J., Gendron-Maguire M., Greenspan R. J., McMahon A. P., Gridley T. Expression pattern of Motch, a mouse homolog of Drosophila Notch, suggests an important role in early postimplantation mouse development. Development. 1992 Jul;115(3):737–744. doi: 10.1242/dev.115.3.737. [DOI] [PubMed] [Google Scholar]
  10. Ellisen L. W., Bird J., West D. C., Soreng A. L., Reynolds T. C., Smith S. D., Sklar J. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell. 1991 Aug 23;66(4):649–661. doi: 10.1016/0092-8674(91)90111-b. [DOI] [PubMed] [Google Scholar]
  11. Fehon R. G., Johansen K., Rebay I., Artavanis-Tsakonas S. Complex cellular and subcellular regulation of notch expression during embryonic and imaginal development of Drosophila: implications for notch function. J Cell Biol. 1991 May;113(3):657–669. doi: 10.1083/jcb.113.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fehon R. G., Kooh P. J., Rebay I., Regan C. L., Xu T., Muskavitch M. A., Artavanis-Tsakonas S. Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila. Cell. 1990 May 4;61(3):523–534. doi: 10.1016/0092-8674(90)90534-l. [DOI] [PubMed] [Google Scholar]
  13. Fietz M. J., Presland R. B., Rogers G. E. The cDNA-deduced amino acid sequence for trichohyalin, a differentiation marker in the hair follicle, contains a 23 amino acid repeat. J Cell Biol. 1990 Feb;110(2):427–436. doi: 10.1083/jcb.110.2.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Greenwald I., Rubin G. M. Making a difference: the role of cell-cell interactions in establishing separate identities for equivalent cells. Cell. 1992 Jan 24;68(2):271–281. doi: 10.1016/0092-8674(92)90470-w. [DOI] [PubMed] [Google Scholar]
  15. Hardy M. H. The secret life of the hair follicle. Trends Genet. 1992 Feb;8(2):55–61. doi: 10.1016/0168-9525(92)90350-d. [DOI] [PubMed] [Google Scholar]
  16. Harland R. M. In situ hybridization: an improved whole-mount method for Xenopus embryos. Methods Cell Biol. 1991;36:685–695. doi: 10.1016/s0091-679x(08)60307-6. [DOI] [PubMed] [Google Scholar]
  17. Heitzler P., Simpson P. The choice of cell fate in the epidermis of Drosophila. Cell. 1991 Mar 22;64(6):1083–1092. doi: 10.1016/0092-8674(91)90263-x. [DOI] [PubMed] [Google Scholar]
  18. Ibrahim L., Wright E. A. A quantitative study of hair growth using mouse and rat vibrissal follicles. I. Dermal papilla volume determines hair volume. J Embryol Exp Morphol. 1982 Dec;72:209–224. [PubMed] [Google Scholar]
  19. Jahoda C. A. Induction of follicle formation and hair growth by vibrissa dermal papillae implanted into rat ear wounds: vibrissa-type fibres are specified. Development. 1992 Aug;115(4):1103–1109. doi: 10.1242/dev.115.4.1103. [DOI] [PubMed] [Google Scholar]
  20. Kanno Y., Takeda K., Daikoku S. Development of the hair in the rat: in vivo and in transplanted tissue. J Dermatol. 1991 May;18(5):262–270. doi: 10.1111/j.1346-8138.1991.tb03080.x. [DOI] [PubMed] [Google Scholar]
  21. Kopan R., Fuchs E. A new look into an old problem: keratins as tools to investigate determination, morphogenesis, and differentiation in skin. Genes Dev. 1989 Jan;3(1):1–15. doi: 10.1101/gad.3.1.1. [DOI] [PubMed] [Google Scholar]
  22. LaMarco K., Thompson C. C., Byers B. P., Walton E. M., McKnight S. L. Identification of Ets- and notch-related subunits in GA binding protein. Science. 1991 Aug 16;253(5021):789–792. doi: 10.1126/science.1876836. [DOI] [PubMed] [Google Scholar]
  23. Linsenmayer T. F. Control of integumentary patterns in the chick. Dev Biol. 1972 Feb;27(2):244–271. doi: 10.1016/0012-1606(72)90101-7. [DOI] [PubMed] [Google Scholar]
  24. Lis J. T. Fractionation of DNA fragments by polyethylene glycol induced precipitation. Methods Enzymol. 1980;65(1):347–353. doi: 10.1016/s0076-6879(80)65044-7. [DOI] [PubMed] [Google Scholar]
  25. Oliver R. F., Jahoda C. A. Dermal-epidermal interactions. Clin Dermatol. 1988 Oct-Dec;6(4):74–82. doi: 10.1016/0738-081x(88)90069-7. [DOI] [PubMed] [Google Scholar]
  26. Rebay I., Fleming R. J., Fehon R. G., Cherbas L., Cherbas P., Artavanis-Tsakonas S. Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell. 1991 Nov 15;67(4):687–699. doi: 10.1016/0092-8674(91)90064-6. [DOI] [PubMed] [Google Scholar]
  27. Rentrop M., Knapp B., Winter H., Schweizer J. Aminoalkylsilane-treated glass slides as support for in situ hybridization of keratin cDNAs to frozen tissue sections under varying fixation and pretreatment conditions. Histochem J. 1986 May;18(5):271–276. doi: 10.1007/BF01676237. [DOI] [PubMed] [Google Scholar]
  28. Ruohola H., Bremer K. A., Baker D., Swedlow J. R., Jan L. Y., Jan Y. N. Role of neurogenic genes in establishment of follicle cell fate and oocyte polarity during oogenesis in Drosophila. Cell. 1991 Aug 9;66(3):433–449. doi: 10.1016/0092-8674(81)90008-8. [DOI] [PubMed] [Google Scholar]
  29. Rupp R. A., Weintraub H. Ubiquitous MyoD transcription at the midblastula transition precedes induction-dependent MyoD expression in presumptive mesoderm of X. laevis. Cell. 1991 Jun 14;65(6):927–937. doi: 10.1016/0092-8674(91)90545-a. [DOI] [PubMed] [Google Scholar]
  30. Sengel P. Pattern formation in skin development. Int J Dev Biol. 1990 Mar;34(1):33–50. [PubMed] [Google Scholar]
  31. Stifani S., Blaumueller C. M., Redhead N. J., Hill R. E., Artavanis-Tsakonas S. Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nat Genet. 1992 Oct;2(2):119–127. doi: 10.1038/ng1092-119. [DOI] [PubMed] [Google Scholar]
  32. Stuart E. S., Garber B., Moscona A. A. Analysis of feather germ formation in the embryo and vitro, in normal development and in skin treated with hydrocortisone. J Exp Zool. 1972 Jan;179(1):97–118. doi: 10.1002/jez.1401790108. [DOI] [PubMed] [Google Scholar]
  33. Stuart E. S., Moscona A. A. Embryonic morphogenesis: role of fibrous lattice in the development of feathers and feather patterns. Science. 1967 Aug 25;157(3791):947–948. doi: 10.1126/science.157.3791.947-a. [DOI] [PubMed] [Google Scholar]
  34. Tapscott S. J., Davis R. L., Thayer M. J., Cheng P. F., Weintraub H., Lassar A. B. MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science. 1988 Oct 21;242(4877):405–411. doi: 10.1126/science.3175662. [DOI] [PubMed] [Google Scholar]
  35. Tezuka M., Ito M., Ito K., Sato Y. Cell kinetic study of human and mouse hair tissues using anti-bromodeoxyuridine monoclonal antibody. J Dermatol Sci. 1990 Sep;1(5):335–346. doi: 10.1016/0923-1811(90)90590-a. [DOI] [PubMed] [Google Scholar]
  36. Wang Y., Benezra R., Sassoon D. A. Id expression during mouse development: a role in morphogenesis. Dev Dyn. 1992 Jul;194(3):222–230. doi: 10.1002/aja.1001940307. [DOI] [PubMed] [Google Scholar]
  37. Weinmaster G., Roberts V. J., Lemke G. A homolog of Drosophila Notch expressed during mammalian development. Development. 1991 Sep;113(1):199–205. doi: 10.1242/dev.113.1.199. [DOI] [PubMed] [Google Scholar]
  38. Wessells N. K. Morphology and proliferation during early feather development. Dev Biol. 1965 Aug;12(1):131–153. doi: 10.1016/0012-1606(65)90025-4. [DOI] [PubMed] [Google Scholar]
  39. Yochem J., Greenwald I. glp-1 and lin-12, genes implicated in distinct cell-cell interactions in C. elegans, encode similar transmembrane proteins. Cell. 1989 Aug 11;58(3):553–563. doi: 10.1016/0092-8674(89)90436-4. [DOI] [PubMed] [Google Scholar]
  40. de Celis J. F., Marí-Beffa M., García-Bellido A. Cell-autonomous role of Notch, an epidermal growth factor homologue, in sensory organ differentiation in Drosophila. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):632–636. doi: 10.1073/pnas.88.2.632. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES