Roux's archives of developmental biology

, Volume 199, Issue 4, pp 189–206 | Cite as

Phenotypic and developmental analysis of mutations at thecrumbs locus, a gene required for the development of epithelia inDrosophila melanogaster

  • Ulrich Tepaß
  • Elisabeth Knust


The genecrumbs (crb) ofDrosophila melanogaster provides an essential function for the embryonic development of ectodermally derived epithelia. Complete loss of function alleles of thecrb gene are recessive embryonic lethals and lead to a disorganization of the primordia of these epithelia, followed by cell death in some tissues. Incrb mutant embryos, different organs are affected to a different extent. Some tissues die almost completely (as the epidermis, the atrium and the pharynx) while others partially survive and conserve their basic epithelial structure (as the tracheal system, the oesophagus, the proventriculus, the salivary glands, the hindgut and the Malpighian tubules). Degeneration is first visible at stage 11 and continues successively throughout development. There is evidence that the loss of epithelial cell polarity may be the cause for the degeneration of these tissues, suggesting that thecrb gene product is involved in stabilizing the apico-basal polarity of epithelial cells. As previously shown, thecrb protein is specifically expressed on the apical side of embryonic epithelia in a reticular pattern outlining the borders of the cells. Here we demonstrate that thecrb protein shows the same subcellular localization in epithelial cells of imaginal discs and in follicle cells, indicating a similar function ofcrb during the development of embryonic, imaginal and follicle epithelia. Clonal analysis experiments indicate that the genecrb is not cell-autonomous in its expression, suggesting that the gene product may act as a diffusible factor and may serve as a signal in a cell-cell communication process. This signal is thought to be required for the formation and/or maintenance of the cell and tissue structure of the respective epithelia.

Key words

Crumbs Drosophila Epithelial development Cell death Cell polarity Non autonomous behaviour 


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  1. Akam M (1987) The molecular basis for metameric pattern in theDrosophila embryo. Development 101:1–22Google Scholar
  2. Anderson KV (1987) Dorsal-ventral embryonic pattern genes ofDrosophila. TIG 3:91–97Google Scholar
  3. Becker HJ (1957) Über Röntgenmosaikflecken und Defektmutationen im Auge vonDrosophila und die Entwicklungsphysiologie des Auges. Zeitschrift für indukt. Abstammungs- und Vererbungslehre 88:333–373Google Scholar
  4. Becker HJ (1976) Mitotic Recombination. In: Ashburner M, Wright TRF (eds) The genetics and biology ofDrosophila, vol 1c. Academic Press, New York, pp 1020–1089Google Scholar
  5. Bier E, Vässin H, Shepherd S, Lee K, McCall K, Barbel S, Ackerman L, Carretto R, Uemura T, Grell E, Jan LY, Jan YN (1989) Searching for pattern and mutations in theDrosophila genome with a P-lacZ vector. Gen Dev 3:1273–1287Google Scholar
  6. Campos-Ortega JA, Hartenstein V (1985) The embryonic development ofDrosophila melanogaster. Springer, Berlin Heidelberg New York TokyoGoogle Scholar
  7. Demerec M (Ed.) (1950) Biology ofDrosophila. John Wiley & Sons Inc, New YorkGoogle Scholar
  8. Doolittle RF, Feng DF, Johnson MS (1984) Computer-based characterization of epidermal growth factor precursor. Nature 307:558–560PubMedGoogle Scholar
  9. Dura JM, Randsholt NB, Deatrick J, Erk I, Santamaria P, Freeman JD, Freeman SJ, Weddell D, Brock HW (1987) A complex genetic locus,polyhomeotic, is required for segmental specification and epidermal development inD. melanogaster. Cell 51:829–839Google Scholar
  10. Ekblom P (1989) Developmentally regulated conversion of mesenchym to epithelium. The FASEB J 3:2141 2150Google Scholar
  11. Elkins T, Zinn K, McAllister L, Hoffmann FM, Goodman CS (1990) Genetic analysis of aDrosophila neural cell adhesion molecule: Interaction of fasciclin I and Abelson tyrosine kinase mutations. Cell 60:565–575PubMedGoogle Scholar
  12. Fleming TP, Johnson MH (1988) From egg to epithelium. Ann Rev Cell Biol 4:459–485PubMedGoogle Scholar
  13. Foe VE (1989) Mitotic domains reveal early commitment of cells inDrosophila embryos. Development 107:1–22Google Scholar
  14. Fujita SJ, Zipursky SL, Benzer S, Ferrus A, Shotwell SL (1982) Monoclonal antibodies against theDrosophila nervous system. Proc Natl Acad Sci USA 79:7929–7933PubMedGoogle Scholar
  15. Garcia-Bellido A, Merriam JR (1971) Genetic analysis of cell heredity in imaginal discs ofDrosophila melanogaster. Proc Natl Acad Sci USA 68:2222–2226PubMedGoogle Scholar
  16. Ghysen A, O'Kane C (1989) Neural enhancer-like elements are specific cell markers inDrosophila. Development 105:35–52PubMedGoogle Scholar
  17. Gray A, Dull TJ, Ullrich A (1983) The nucleotide sequence of epidermal growth factor cDNA predicts a 128000 molecular weight precursor. Nature 303:722–725PubMedGoogle Scholar
  18. Hartenstein V (1987) The influence of segmental compartmentalisation on the development of the larval peripheral nervous system inDrosophila melanogaster. Roux's Arch Dev Biol 196:101–112Google Scholar
  19. Hartenstein V (1988) Development ofDrosophila larval sensory organs: spatiotemporal pattern of sensory neurones, peripheral axonal pathways and sensilla differentiation. Development 102:869–886Google Scholar
  20. Ingham PW (1988) The molecular genetics of embryonic pattern formation inDrosophila. Nature 335:25–34PubMedGoogle Scholar
  21. Jan LY, Jan YN (1982) Antibodies to horseradish peroxidase as specific neuronal markers inDrosophila and in grasshopper embryos. Proc Natl Acad Sci USA 72:2700–2704Google Scholar
  22. Jürgens G, Wieschaus E, Nüsslein-Volhard C, Kluding H (1984) Mutations affecting the pattern of larval cuticle inDrosophila melanogaster. II. Zygotic loci on the third chromosome. Roux's Arch Dev Biol 193:283–295Google Scholar
  23. King RC (1970) Ovarian development inDrosophila melanogaster. Academic Press, New York London San FranciscoGoogle Scholar
  24. Klein G, Langegger M, Timpl R, Ekblom P (1988) Role of laminin A chain in the development of epithelial cell polarity. Cell 55:331–341PubMedGoogle Scholar
  25. Klingensmith J, Noll E, Perrimon N (1989) The segment polarity phenotype ofDrosophila involves differential tendencies toward transformation and cell death. Dev Biol 134:130–145PubMedGoogle Scholar
  26. Knust E, Dietrich U, Tepaß U, Bremer KA, Weigel D, Vässin H, Campos-Ortega JA (1987a) EGF homologous sequences encoded in the genome ofDrosophila melanogaster, and their relation to neurogenic genes. EMBO J 6:761–766PubMedGoogle Scholar
  27. Knust E, Bremer KA, Vässin H, Ziemer A, Tepaß U, Campos-Ortega JA (1987b) TheEnhancer of split locus and neurogenesis inDrosophila melanogaster. Dev Biol 122:262–273PubMedGoogle Scholar
  28. Lehmann R, Nüsslein-Volhard C (1987)hunchback, a gene required for segmentation of the anterior and posterior region of theDrosophila embryo. Dev Biol 119:402–417PubMedGoogle Scholar
  29. Lewis EB (1978) A gene complex controlling segmentation inDrosophila. Nature 276:565–570PubMedGoogle Scholar
  30. Lindsley DL, Grell EH (1968) Genetic variations ofDrosophila melanogaster. Carnegie Inst Publ no 627, Washington DCGoogle Scholar
  31. Lindsley DL, Zimm G (1985) The genome ofDrosophila melanogaster. Drosophila Inform Serv 62Google Scholar
  32. Lindsley DL, Zimm G (1990) The genome ofDrosophila melanogaster. Drosophila Inform Serv 68Google Scholar
  33. Livneh E, Glaser L, Segal D, Schlessinger J, Shilo BZ (1985) TheDrosophila EGF receptor homolog: conservation of both hormone binding and kinase domain. Cell 40:599–607PubMedGoogle Scholar
  34. Madhaven MM, Schneiderman HA (1977) Histological analysis of the dynamics of growth of imaginal discs and histoblast nests during the larval development ofDrosophila melanogaster. Roux's Arch Dev Biol 183:269–305Google Scholar
  35. Magrassi L, Lawrence PA (1988) The pattern of cell death infushi tarazu, a segmentation gene ofDrosophila. Development 104:447–451PubMedGoogle Scholar
  36. Martinez-Arias A (1985) The development offused-embryos ofDrosophila melanogaster. J Embryol Exp Morphol 87:99–114PubMedGoogle Scholar
  37. Martinez-Arias A (1989) A cellular basis for pattern formation in the insect epidermis. TIG 5:262–267PubMedGoogle Scholar
  38. Nüsslein-Volhard C, Frohnhöfer HG, Lehmann R (1987) Determination of anteroposterior polarity inDrosophila. Science 238:1675–1681PubMedGoogle Scholar
  39. Perrimon N, Gans M (1983) Clonal analysis of the tissue specificity of recessive female-sterile mutations ofDrosophila melanogaster using a dominant female-sterile mutationFs(1) K1237. Dev Biol 100:365–373PubMedGoogle Scholar
  40. Poodry CA (1980) Epidermis: Morphology and Development. In: Ashburner M, Wright TRF (eds) The genetics and biology of Drosophila, vol 2d. Academic Press, New York, pp 443–498Google Scholar
  41. Price JV, Clifford RJ, Schüpbach T (1989) The maternal ventralizing locustorpedo is allelic tofaint little ball, an embryonic lethal, and encodes theDrosophila EGF receptor homolog. Cell 56:1085–1092PubMedGoogle Scholar
  42. Riggelman B, Wieschaus E, Scheld P (1989) Molecular analysis of thearmadillo locus: uniformly distributed transcripts and a protein with novel internal repeats are associated with aDrosophila segment polarity gene. Gen Dev 3:96–113Google Scholar
  43. Rodriguez-Boulan E, Nelson WJ (1989) Morphogenesis of the polarized epithelial cell phenotype. Science 245:718–725PubMedGoogle Scholar
  44. Scheijter ED, Shilo B-Z (1989) TheDrosophila EGF receptor homolog (DER) gene is allelic tofaint little ball, a locus essential for embryonic development. Cell 56:1093–1104PubMedGoogle Scholar
  45. Schüpbach T (1987) Germ line and soma cooperate during oogenesis to establish the dorsoventral pattern of egg shell and embryo inDrosophila melanogaster. Cell 49:699–707PubMedGoogle Scholar
  46. Scott J, Urdea M, Quiroga M, Sanchez-Pescador R, Fong N, Selby M, Rutter WJ, Bell GI (1983) Structure of a mouse submaxillary messenger RNA encoding epidermal growth factor and seven related proteins. Science 221:236–240PubMedGoogle Scholar
  47. Simons K, Fuller SD (1985) Cell surface polarity in epithelia. Ann Rev Cell Biol 1:243–288PubMedGoogle Scholar
  48. Smouse D, Goodman C, Mahowald A, Perrimon N (1988)polyhomeotic: a gene required for the embryonic development of axon pathways in the central nervous system ofDrosophila. Gen Dev 2:830–842Google Scholar
  49. Smouse D, Perrimon N (1990) Genetic dissection of a complex neurological mutant,polyhomeotic, inDrosophila. Dev Biol 139:169–185PubMedGoogle Scholar
  50. Szabad J, Schüpbach T, Wieschaus E (1979) Cell lineage and development in the larval epidermis ofDrosophila melanogaster. Dev Biol 73:256–271PubMedGoogle Scholar
  51. Tearle R, Nüsslein-Volhard C (1987) Tübingen mutants and stocklist. Drosophila Inform Serv 66:209–269Google Scholar
  52. Technau GM (1987) A single cell approach to problems of cell lineage and commitment during embryogenesis ofDrosophila melanogaster. Development 100:1–12PubMedGoogle Scholar
  53. Tepaß U, Theres C, Knust E (1990) TheDrosophila genecrumbs encodes an EGF-like protein expressed on apical membranes ofDrosophila epithelial cells and required for organization of epithelia. Cell 61:787–799PubMedGoogle Scholar
  54. Tomaselli KJ, Neugebauer KM, Bixby JL, Lilien J, Reichardt LF (1988) N-cadherin and integrins: two receptor systems that mediate neural process outgrowth on astrocyte surfaces. Neuron 1:33–43PubMedGoogle Scholar
  55. Van der Meer J (1977) Optical clean and permanent mount preparations for phase contrast microscopy of cuticular structures of insect larvae. Drosophila Inform Serv 52:160Google Scholar
  56. Weigel D, Jürgens G, Küttner F, Seifert E, Jäckle H (1989a) The homeotic genefork head encodes a nuclear protein and is expressed in the terminal regions of theDrosophila embryo. Cell 57:645–658PubMedGoogle Scholar
  57. Weigel D, Bellen HJ, Jürgens G, Jäckle H (1989b) Primordium specific requirement of the homeotic genefork head in the developing gut of theDrosophila embryo. Roux's Arch Dev Biol 198:201–210Google Scholar
  58. Wieschaus E, Riggleman R (1987) Autonomous requirements for the segment polarity genearmadillo duringDrosophila embryogenesis. Cell 49:177–184PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Ulrich Tepaß
    • 1
  • Elisabeth Knust
    • 1
  1. 1.Institut für EntwicklungsphysiologieUniversität zu KölnKöln 41Federal Republic of Germany

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