Abstract
The Notch gene in Drosophila encodes a transmembrane protein with homology to EGF that appears to mediate cell-cell interactions necessary for proper epidermal vs. neural fate decisions. In this study, we examine Notch expression in detail throughout embryonic and imaginal development using confocal laser-scanning microscopy and specific mAb probes. We find that Notch is expressed in a tissue- specific manner as early as the cellular blastoderm stage, when cells of the presumptive mesoderm clearly express less Notch than adjacent ectodermal precursors. Notch is abundantly expressed during the initial determination of neuronal lineages, such as the embryonic neuroblasts and the precursors of sensory neurons in the imaginal disc epithelia, but expression quickly decreases during subsequent differentiation. These changing patterns of Notch expression do not correlate well with cell movements, and thus do not appear to support the notion that the major function of Notch is to maintain epithelial integrity via adhesive mechanisms. Our data suggest instead that Notch may act as a cell-surface receptor, perhaps functioning in the lateral inhibition mechanism that is necessary for proper spacing of neuronal precursors.
Full Text
The Full Text of this article is available as a PDF (4.6 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Artavanis-Tsakonas S. The molecular biology of the Notch locus and the fine tuning of differentiation in Drosophila. Trends Genet. 1988 Apr;4(4):95–100. doi: 10.1016/0168-9525(88)90096-0. [DOI] [PubMed] [Google Scholar]
- Baker N. E., Mlodzik M., Rubin G. M. Spacing differentiation in the developing Drosophila eye: a fibrinogen-related lateral inhibitor encoded by scabrous. Science. 1990 Dec 7;250(4986):1370–1377. doi: 10.1126/science.2175046. [DOI] [PubMed] [Google Scholar]
- 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]
- Cagan R. L., Ready D. F. The emergence of order in the Drosophila pupal retina. Dev Biol. 1989 Dec;136(2):346–362. doi: 10.1016/0012-1606(89)90261-3. [DOI] [PubMed] [Google Scholar]
- Davis C. G. The many faces of epidermal growth factor repeats. New Biol. 1990 May;2(5):410–419. [PubMed] [Google Scholar]
- Dietrich U., Campos-Ortega J. A. The expression of neurogenic loci in imaginal epidermal cells of Drosophila melanogaster. J Neurogenet. 1984 Dec;1(4):315–332. doi: 10.3109/01677068409107094. [DOI] [PubMed] [Google Scholar]
- Doe C. Q., Goodman C. S. Early events in insect neurogenesis. II. The role of cell interactions and cell lineage in the determination of neuronal precursor cells. Dev Biol. 1985 Sep;111(1):206–219. doi: 10.1016/0012-1606(85)90446-4. [DOI] [PubMed] [Google Scholar]
- 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]
- Fristom D., Fristom J. W. The mechanism of evagination of imaginal discs of Drosophila melanogaster. 1. General considerations. Dev Biol. 1975 Mar;43(1):1–23. doi: 10.1016/0012-1606(75)90127-x. [DOI] [PubMed] [Google Scholar]
- Furie B., Furie B. C. The molecular basis of blood coagulation. Cell. 1988 May 20;53(4):505–518. doi: 10.1016/0092-8674(88)90567-3. [DOI] [PubMed] [Google Scholar]
- Ghysen A., O'Kane C. Neural enhancer-like elements as specific cell markers in Drosophila. Development. 1989 Jan;105(1):35–52. doi: 10.1242/dev.105.1.35. [DOI] [PubMed] [Google Scholar]
- Greenspan R. J. The Notch gene, adhesion, and developmental fate in the Drosophila embryo. New Biol. 1990 Jul;2(7):595–600. [PubMed] [Google Scholar]
- Hartenstein V., Posakony J. W. Development of adult sensilla on the wing and notum of Drosophila melanogaster. Development. 1989 Oct;107(2):389–405. doi: 10.1242/dev.107.2.389. [DOI] [PubMed] [Google Scholar]
- Hartley D. A., Xu T. A., Artavanis-Tsakonas S. The embryonic expression of the Notch locus of Drosophila melanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein. EMBO J. 1987 Nov;6(11):3407–3417. doi: 10.1002/j.1460-2075.1987.tb02664.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hoppe P. E., Greenspan R. J. The Notch locus of Drosophila is required in epidermal cells for epidermal development. Development. 1990 Aug;109(4):875–885. doi: 10.1242/dev.109.4.875. [DOI] [PubMed] [Google Scholar]
- Johansen K. M., Fehon R. G., Artavanis-Tsakonas S. The notch gene product is a glycoprotein expressed on the cell surface of both epidermal and neuronal precursor cells during Drosophila development. J Cell Biol. 1989 Nov;109(5):2427–2440. doi: 10.1083/jcb.109.5.2427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kidd S., Baylies M. K., Gasic G. P., Young M. W. Structure and distribution of the Notch protein in developing Drosophila. Genes Dev. 1989 Aug;3(8):1113–1129. doi: 10.1101/gad.3.8.1113. [DOI] [PubMed] [Google Scholar]
- Kidd S., Kelley M. R., Young M. W. Sequence of the notch locus of Drosophila melanogaster: relationship of the encoded protein to mammalian clotting and growth factors. Mol Cell Biol. 1986 Sep;6(9):3094–3108. doi: 10.1128/mcb.6.9.3094. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kopczynski C. C., Alton A. K., Fechtel K., Kooh P. J., Muskavitch M. A. Delta, a Drosophila neurogenic gene, is transcriptionally complex and encodes a protein related to blood coagulation factors and epidermal growth factor of vertebrates. Genes Dev. 1988 Dec;2(12B):1723–1735. doi: 10.1101/gad.2.12b.1723. [DOI] [PubMed] [Google Scholar]
- Kopczynski C. C., Muskavitch M. A. Complex spatio-temporal accumulation of alternative transcripts from the neurogenic gene Delta during Drosophila embryogenesis. Development. 1989 Nov;107(3):623–636. doi: 10.1242/dev.107.3.623. [DOI] [PubMed] [Google Scholar]
- Leptin M., Grunewald B. Cell shape changes during gastrulation in Drosophila. Development. 1990 Sep;110(1):73–84. doi: 10.1242/dev.110.1.73. [DOI] [PubMed] [Google Scholar]
- Lux S. E., John K. M., Bennett V. Analysis of cDNA for human erythrocyte ankyrin indicates a repeated structure with homology to tissue-differentiation and cell-cycle control proteins. Nature. 1990 Mar 1;344(6261):36–42. doi: 10.1038/344036a0. [DOI] [PubMed] [Google Scholar]
- Markopoulou K., Artavanis-Tsakonas S. The expression of the neurogenic locus Notch during the postembryonic development of Drosophila melanogaster and its relationship to mitotic activity. J Neurogenet. 1989 Sep;6(1):11–26. doi: 10.3109/01677068909107097. [DOI] [PubMed] [Google Scholar]
- Mlodzik M., Baker N. E., Rubin G. M. Isolation and expression of scabrous, a gene regulating neurogenesis in Drosophila. Genes Dev. 1990 Nov;4(11):1848–1861. doi: 10.1101/gad.4.11.1848. [DOI] [PubMed] [Google Scholar]
- Nelson W. J. Topogenesis of plasma membrane domains in polarized epithelial cells. Curr Opin Cell Biol. 1989 Aug;1(4):660–668. doi: 10.1016/0955-0674(89)90031-8. [DOI] [PubMed] [Google Scholar]
- Poulson D. F. Chromosomal Deficiencies and the Embryonic Development of Drosophila Melanogaster. Proc Natl Acad Sci U S A. 1937 Mar;23(3):133–137. doi: 10.1073/pnas.23.3.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ready D. F., Hanson T. E., Benzer S. Development of the Drosophila retina, a neurocrystalline lattice. Dev Biol. 1976 Oct 15;53(2):217–240. doi: 10.1016/0012-1606(76)90225-6. [DOI] [PubMed] [Google Scholar]
- Schubiger M., Palka J. Changing spatial patterns of DNA replication in the developing wing of Drosophila. Dev Biol. 1987 Sep;123(1):145–153. doi: 10.1016/0012-1606(87)90436-2. [DOI] [PubMed] [Google Scholar]
- Shellenbarger D. L., Mohler J. D. Temperature-sensitive periods and autonomy of pleiotropic effects of l(1)Nts1, a conditional notch lethal in Drosophila. Dev Biol. 1978 Feb;62(2):432–446. doi: 10.1016/0012-1606(78)90226-9. [DOI] [PubMed] [Google Scholar]
- Simpson P. Lateral inhibition and the development of the sensory bristles of the adult peripheral nervous system of Drosophila. Development. 1990 Jul;109(3):509–519. doi: 10.1242/dev.109.3.509. [DOI] [PubMed] [Google Scholar]
- Truman J. W., Bate M. Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol. 1988 Jan;125(1):145–157. doi: 10.1016/0012-1606(88)90067-x. [DOI] [PubMed] [Google Scholar]
- Vässin H., Bremer K. A., Knust E., Campos-Ortega J. A. The neurogenic gene Delta of Drosophila melanogaster is expressed in neurogenic territories and encodes a putative transmembrane protein with EGF-like repeats. EMBO J. 1987 Nov;6(11):3431–3440. doi: 10.1002/j.1460-2075.1987.tb02666.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warn R. M., Robert-Nicoud M. F-actin organization during the cellularization of the Drosophila embryo as revealed with a confocal laser scanning microscope. J Cell Sci. 1990 May;96(Pt 1):35–42. doi: 10.1242/jcs.96.1.35. [DOI] [PubMed] [Google Scholar]
- Wharton K. A., Johansen K. M., Xu T., Artavanis-Tsakonas S. Nucleotide sequence from the neurogenic locus notch implies a gene product that shares homology with proteins containing EGF-like repeats. Cell. 1985 Dec;43(3 Pt 2):567–581. doi: 10.1016/0092-8674(85)90229-6. [DOI] [PubMed] [Google Scholar]
- White K., Kankel D. R. Patterns of cell division and cell movement in the formation of the imaginal nervous system in Drosophila melanogaster. Dev Biol. 1978 Aug;65(2):296–321. doi: 10.1016/0012-1606(78)90029-5. [DOI] [PubMed] [Google Scholar]
- Wright T. R. The genetics of embryogenesis in Drosophila. Adv Genet. 1970;15:261–395. doi: 10.1016/s0065-2660(08)60075-9. [DOI] [PubMed] [Google Scholar]
- Xu T., Rebay I., Fleming R. J., Scottgale T. N., Artavanis-Tsakonas S. The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. Genes Dev. 1990 Mar;4(3):464–475. doi: 10.1101/gad.4.3.464. [DOI] [PubMed] [Google Scholar]
- Zipursky S. L., Venkatesh T. R., Teplow D. B., Benzer S. Neuronal development in the Drosophila retina: monoclonal antibodies as molecular probes. Cell. 1984 Jan;36(1):15–26. doi: 10.1016/0092-8674(84)90069-2. [DOI] [PubMed] [Google Scholar]