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. 2000 Dec;156(4):1817–1828. doi: 10.1093/genetics/156.4.1817

The tricornered gene, which is required for the integrity of epidermal cell extensions, encodes the Drosophila nuclear DBF2-related kinase.

W Geng 1, B He 1, M Wang 1, P N Adler 1
PMCID: PMC1461384  PMID: 11102376

Abstract

During their differentiation epidermal cells of Drosophila form a rich variety of polarized structures. These include the epidermal hairs that decorate much of the adult cuticular surface, the shafts of the bristle sense organs, the lateral extensions of the arista, and the larval denticles. These cuticular structures are produced by cytoskeletal-mediated outgrowths of epidermal cells. Mutations in the tricornered gene result in the splitting or branching of all of these structures. Thus, tricornered function appears to be important for maintaining the integrity of the outgrowths. tricornered mutations however do not have major effects on the growth or shape of these cellular extensions. Inhibiting actin polymerization in differentiating cells by cytochalasin D or latrunculin A treatment also induces the splitting of hairs and bristles, suggesting that the actin cytoskeleton might be a target of tricornered. However, the drugs also result in short, fat, and occasionally malformed hairs and bristles. The data suggest that the function of the actin cytoskeleton is important for maintaining the integrity of cellular extensions as well as their growth and shape. Thus, if tricornered causes the splitting of cellular extensions by interacting with the actin cytoskeleton it likely does so in a subtle way. Consistent with this possibility we found that a weak tricornered mutant is hypersensitive to cytochalasin D. We have cloned the tricornered gene and found that it encodes the Drosophila NDR kinase. This is a conserved ser/thr protein kinase found in Caenorhabditis elegans and humans that is related to a number of kinases that have been found to be important in controlling cell structure and proliferation.

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Selected References

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  1. Ashburner M., Misra S., Roote J., Lewis S. E., Blazej R., Davis T., Doyle C., Galle R., George R., Harris N. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999 Sep;153(1):179–219. doi: 10.1093/genetics/153.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brand A. H., Perrimon N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development. 1993 Jun;118(2):401–415. doi: 10.1242/dev.118.2.401. [DOI] [PubMed] [Google Scholar]
  3. Brook J. D., McCurrach M. E., Harley H. G., Buckler A. J., Church D., Aburatani H., Hunter K., Stanton V. P., Thirion J. P., Hudson T. Molecular basis of myotonic dystrophy: expansion of a trinucleotide (CTG) repeat at the 3' end of a transcript encoding a protein kinase family member. Cell. 1992 Feb 21;68(4):799–808. doi: 10.1016/0092-8674(92)90154-5. [DOI] [PubMed] [Google Scholar]
  4. Bryan J., Edwards R., Matsudaira P., Otto J., Wulfkuhle J. Fascin, an echinoid actin-bundling protein, is a homolog of the Drosophila singed gene product. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9115–9119. doi: 10.1073/pnas.90.19.9115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cant K., Knowles B. A., Mooseker M. S., Cooley L. Drosophila singed, a fascin homolog, is required for actin bundle formation during oogenesis and bristle extension. J Cell Biol. 1994 Apr;125(2):369–380. doi: 10.1083/jcb.125.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Castellano F., Montcourrier P., Guillemot J. C., Gouin E., Machesky L., Cossart P., Chavrier P. Inducible recruitment of Cdc42 or WASP to a cell-surface receptor triggers actin polymerization and filopodium formation. Curr Biol. 1999 Apr 8;9(7):351–360. doi: 10.1016/s0960-9822(99)80161-4. [DOI] [PubMed] [Google Scholar]
  7. Deák P., Omar M. M., Saunders R. D., Pál M., Komonyi O., Szidonya J., Maróy P., Zhang Y., Ashburner M., Benos P. P-element insertion alleles of essential genes on the third chromosome of Drosophila melanogaster: correlation of physical and cytogenetic maps in chromosomal region 86E-87F. Genetics. 1997 Dec;147(4):1697–1722. doi: 10.1093/genetics/147.4.1697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eaton S. Planar polarization of Drosophila and vertebrate epithelia. Curr Opin Cell Biol. 1997 Dec;9(6):860–866. doi: 10.1016/s0955-0674(97)80089-0. [DOI] [PubMed] [Google Scholar]
  9. Eaton S., Wepf R., Simons K. Roles for Rac1 and Cdc42 in planar polarization and hair outgrowth in the wing of Drosophila. J Cell Biol. 1996 Dec;135(5):1277–1289. doi: 10.1083/jcb.135.5.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fu Y. H., Friedman D. L., Richards S., Pearlman J. A., Gibbs R. A., Pizzuti A., Ashizawa T., Perryman M. B., Scarlato G., Fenwick R. G., Jr Decreased expression of myotonin-protein kinase messenger RNA and protein in adult form of myotonic dystrophy. Science. 1993 Apr 9;260(5105):235–238. doi: 10.1126/science.8469976. [DOI] [PubMed] [Google Scholar]
  11. Gho M., Schweisguth F. Frizzled signalling controls orientation of asymmetric sense organ precursor cell divisions in Drosophila. Nature. 1998 May 14;393(6681):178–181. doi: 10.1038/30265. [DOI] [PubMed] [Google Scholar]
  12. Gubb D., García-Bellido A. A genetic analysis of the determination of cuticular polarity during development in Drosophila melanogaster. J Embryol Exp Morphol. 1982 Apr;68:37–57. [PubMed] [Google Scholar]
  13. Hanks S. K., Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification. FASEB J. 1995 May;9(8):576–596. [PubMed] [Google Scholar]
  14. Justice R. W., Zilian O., Woods D. F., Noll M., Bryant P. J. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 1995 Mar 1;9(5):534–546. doi: 10.1101/gad.9.5.534. [DOI] [PubMed] [Google Scholar]
  15. Kennerdell J. R., Carthew R. W. Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell. 1998 Dec 23;95(7):1017–1026. doi: 10.1016/s0092-8674(00)81725-0. [DOI] [PubMed] [Google Scholar]
  16. Komarnitsky S. I., Chiang Y. C., Luca F. C., Chen J., Toyn J. H., Winey M., Johnston L. H., Denis C. L. DBF2 protein kinase binds to and acts through the cell cycle-regulated MOB1 protein. Mol Cell Biol. 1998 Apr;18(4):2100–2107. doi: 10.1128/mcb.18.4.2100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leung T., Chen X. Q., Manser E., Lim L. The p160 RhoA-binding kinase ROK alpha is a member of a kinase family and is involved in the reorganization of the cytoskeleton. Mol Cell Biol. 1996 Oct;16(10):5313–5327. doi: 10.1128/mcb.16.10.5313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Luo L., Lee T., Tsai L., Tang G., Jan L. Y., Jan Y. N. Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):12963–12968. doi: 10.1073/pnas.94.24.12963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McMillan J. N., Sia R. A., Lew D. J. A morphogenesis checkpoint monitors the actin cytoskeleton in yeast. J Cell Biol. 1998 Sep 21;142(6):1487–1499. doi: 10.1083/jcb.142.6.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Millward T. A., Hess D., Hemmings B. A. Ndr protein kinase is regulated by phosphorylation on two conserved sequence motifs. J Biol Chem. 1999 Nov 26;274(48):33847–33850. doi: 10.1074/jbc.274.48.33847. [DOI] [PubMed] [Google Scholar]
  21. Nobes C. D., Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995 Apr 7;81(1):53–62. doi: 10.1016/0092-8674(95)90370-4. [DOI] [PubMed] [Google Scholar]
  22. Petersen N. S., Lankenau D. H., Mitchell H. K., Young P., Corces V. G. forked proteins are components of fiber bundles present in developing bristles of Drosophila melanogaster. Genetics. 1994 Jan;136(1):173–182. doi: 10.1093/genetics/136.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Spector I., Braet F., Shochet N. R., Bubb M. R. New anti-actin drugs in the study of the organization and function of the actin cytoskeleton. Microsc Res Tech. 1999 Oct 1;47(1):18–37. doi: 10.1002/(SICI)1097-0029(19991001)47:1<18::AID-JEMT3>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  24. Tapon N., Hall A. Rho, Rac and Cdc42 GTPases regulate the organization of the actin cytoskeleton. Curr Opin Cell Biol. 1997 Feb;9(1):86–92. doi: 10.1016/s0955-0674(97)80156-1. [DOI] [PubMed] [Google Scholar]
  25. Tilney L. G., Connelly P. S., Vranich K. A., Shaw M. K., Guild G. M. Actin filaments and microtubules play different roles during bristle elongation in Drosophila. J Cell Sci. 2000 Apr;113(Pt 7):1255–1265. doi: 10.1242/jcs.113.7.1255. [DOI] [PubMed] [Google Scholar]
  26. Tilney L. G., Connelly P. S., Vranich K. A., Shaw M. K., Guild G. M. Regulation of actin filament cross-linking and bundle shape in Drosophila bristles. J Cell Biol. 2000 Jan 10;148(1):87–100. doi: 10.1083/jcb.148.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tilney L. G., Connelly P. S., Vranich K. A., Shaw M. K., Guild G. M. Why are two different cross-linkers necessary for actin bundle formation in vivo and what does each cross-link contribute? J Cell Biol. 1998 Oct 5;143(1):121–133. doi: 10.1083/jcb.143.1.121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tilney L. G., Tilney M. S., Guild G. M. F actin bundles in Drosophila bristles. I. Two filament cross-links are involved in bundling. J Cell Biol. 1995 Aug;130(3):629–638. doi: 10.1083/jcb.130.3.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Turner C. M., Adler P. N. Distinct roles for the actin and microtubule cytoskeletons in the morphogenesis of epidermal hairs during wing development in Drosophila. Mech Dev. 1998 Jan;70(1-2):181–192. doi: 10.1016/s0925-4773(97)00194-9. [DOI] [PubMed] [Google Scholar]
  30. Verde F., Wiley D. J., Nurse P. Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle. Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7526–7531. doi: 10.1073/pnas.95.13.7526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Vinson C. R., Adler P. N. Directional non-cell autonomy and the transmission of polarity information by the frizzled gene of Drosophila. Nature. 1987 Oct 8;329(6139):549–551. doi: 10.1038/329549a0. [DOI] [PubMed] [Google Scholar]
  32. Wong L. L., Adler P. N. Tissue polarity genes of Drosophila regulate the subcellular location for prehair initiation in pupal wing cells. J Cell Biol. 1993 Oct;123(1):209–221. doi: 10.1083/jcb.123.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Xu T., Wang W., Zhang S., Stewart R. A., Yu W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development. 1995 Apr;121(4):1053–1063. doi: 10.1242/dev.121.4.1053. [DOI] [PubMed] [Google Scholar]
  34. Yarden O., Plamann M., Ebbole D. J., Yanofsky C. cot-1, a gene required for hyphal elongation in Neurospora crassa, encodes a protein kinase. EMBO J. 1992 Jun;11(6):2159–2166. doi: 10.1002/j.1460-2075.1992.tb05275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]

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