Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1999 Jun;152(2):629–640. doi: 10.1093/genetics/152.2.629

Genetic analysis of the bone morphogenetic protein-related gene, gbb, identifies multiple requirements during Drosophila development.

K A Wharton 1, J M Cook 1, S Torres-Schumann 1, K de Castro 1, E Borod 1, D A Phillips 1
PMCID: PMC1460618  PMID: 10353905

Abstract

We have isolated mutations in the Drosophila melanogaster gene glass bottom boat (gbb), which encodes a TGF-beta signaling molecule (formerly referred to as 60A) with highest sequence similarity to members of the bone morphogenetic protein (BMP) subgroup including vertebrate BMPs 5-8. Genetic analysis of both null and hypomorphic gbb alleles indicates that the gene is required in many developmental processes, including embryonic midgut morphogenesis, patterning of the larval cuticle, fat body morphology, and development and patterning of the imaginal discs. In the embryonic midgut, we show that gbb is required for the formation of the anterior constriction and for maintenance of the homeotic gene Antennapedia in the visceral mesoderm. In addition, we show a requirement for gbb in the anterior and posterior cells of the underlying endoderm and in the formation and extension of the gastric caecae. gbb is required in all the imaginal discs for proper disc growth and for specification of veins in the wing and of macrochaete in the notum. Significantly, some of these tissues have been shown to also require the Drosophila BMP2/4 homolog decapentaplegic (dpp), while others do not. These results indicate that signaling by both gbb and dpp may contribute to the development of some tissues, while in others, gbb may signal independently of dpp.

Full Text

The Full Text of this article is available as a PDF (271.1 KB).

Selected References

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

  1. Aono A., Hazama M., Notoya K., Taketomi S., Yamasaki H., Tsukuda R., Sasaki S., Fujisawa Y. Potent ectopic bone-inducing activity of bone morphogenetic protein-4/7 heterodimer. Biochem Biophys Res Commun. 1995 May 25;210(3):670–677. doi: 10.1006/bbrc.1995.1712. [DOI] [PubMed] [Google Scholar]
  2. Arora K., Levine M. S., O'Connor M. B. The screw gene encodes a ubiquitously expressed member of the TGF-beta family required for specification of dorsal cell fates in the Drosophila embryo. Genes Dev. 1994 Nov 1;8(21):2588–2601. doi: 10.1101/gad.8.21.2588. [DOI] [PubMed] [Google Scholar]
  3. Bienz M. Homeotic genes and positional signalling in the Drosophila viscera. Trends Genet. 1994 Jan;10(1):22–26. doi: 10.1016/0168-9525(94)90015-9. [DOI] [PubMed] [Google Scholar]
  4. Bilder D., Graba Y., Scott M. P. Wnt and TGFbeta signals subdivide the AbdA Hox domain during Drosophila mesoderm patterning. Development. 1998 May;125(9):1781–1790. doi: 10.1242/dev.125.9.1781. [DOI] [PubMed] [Google Scholar]
  5. Brummel T. J., Twombly V., Marqués G., Wrana J. L., Newfeld S. J., Attisano L., Massagué J., O'Connor M. B., Gelbart W. M. Characterization and relationship of Dpp receptors encoded by the saxophone and thick veins genes in Drosophila. Cell. 1994 Jul 29;78(2):251–261. doi: 10.1016/0092-8674(94)90295-x. [DOI] [PubMed] [Google Scholar]
  6. Campbell G., Weaver T., Tomlinson A. Axis specification in the developing Drosophila appendage: the role of wingless, decapentaplegic, and the homeobox gene aristaless. Cell. 1993 Sep 24;74(6):1113–1123. doi: 10.1016/0092-8674(93)90732-6. [DOI] [PubMed] [Google Scholar]
  7. Cavener D. R. Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates. Nucleic Acids Res. 1987 Feb 25;15(4):1353–1361. doi: 10.1093/nar/15.4.1353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cho K. W., Blitz I. L. BMPs, Smads and metalloproteases: extracellular and intracellular modes of negative regulation. Curr Opin Genet Dev. 1998 Aug;8(4):443–449. doi: 10.1016/s0959-437x(98)80116-0. [DOI] [PubMed] [Google Scholar]
  9. Chou T. B., Noll E., Perrimon N. Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras. Development. 1993 Dec;119(4):1359–1369. doi: 10.1242/dev.119.4.1359. [DOI] [PubMed] [Google Scholar]
  10. Cohen S. M. Specification of limb development in the Drosophila embryo by positional cues from segmentation genes. Nature. 1990 Jan 11;343(6254):173–177. doi: 10.1038/343173a0. [DOI] [PubMed] [Google Scholar]
  11. Daopin S., Piez K. A., Ogawa Y., Davies D. R. Crystal structure of transforming growth factor-beta 2: an unusual fold for the superfamily. Science. 1992 Jul 17;257(5068):369–373. doi: 10.1126/science.1631557. [DOI] [PubMed] [Google Scholar]
  12. Das P., Maduzia L. L., Wang H., Finelli A. L., Cho S. H., Smith M. M., Padgett R. W. The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling. Development. 1998 Apr;125(8):1519–1528. doi: 10.1242/dev.125.8.1519. [DOI] [PubMed] [Google Scholar]
  13. Doctor J. S., Jackson P. D., Rashka K. E., Visalli M., Hoffmann F. M. Sequence, biochemical characterization, and developmental expression of a new member of the TGF-beta superfamily in Drosophila melanogaster. Dev Biol. 1992 Jun;151(2):491–505. doi: 10.1016/0012-1606(92)90188-m. [DOI] [PubMed] [Google Scholar]
  14. Dudley A. T., Robertson E. J. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev Dyn. 1997 Mar;208(3):349–362. doi: 10.1002/(SICI)1097-0177(199703)208:3<349::AID-AJA6>3.0.CO;2-I. [DOI] [PubMed] [Google Scholar]
  15. Griffith D. L., Keck P. C., Sampath T. K., Rueger D. C., Carlson W. D. Three-dimensional structure of recombinant human osteogenic protein 1: structural paradigm for the transforming growth factor beta superfamily. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):878–883. doi: 10.1073/pnas.93.2.878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Haerry T. E., Khalsa O., O'Connor M. B., Wharton K. A. Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila. Development. 1998 Oct;125(20):3977–3987. doi: 10.1242/dev.125.20.3977. [DOI] [PubMed] [Google Scholar]
  17. Hudson J. B., Podos S. D., Keith K., Simpson S. L., Ferguson E. L. The Drosophila Medea gene is required downstream of dpp and encodes a functional homolog of human Smad4. Development. 1998 Apr;125(8):1407–1420. doi: 10.1242/dev.125.8.1407. [DOI] [PubMed] [Google Scholar]
  18. Immerglück K., Lawrence P. A., Bienz M. Induction across germ layers in Drosophila mediated by a genetic cascade. Cell. 1990 Jul 27;62(2):261–268. doi: 10.1016/0092-8674(90)90364-k. [DOI] [PubMed] [Google Scholar]
  19. Khalsa O., Yoon J. W., Torres-Schumann S., Wharton K. A. TGF-beta/BMP superfamily members, Gbb-60A and Dpp, cooperate to provide pattern information and establish cell identity in the Drosophila wing. Development. 1998 Jul;125(14):2723–2734. doi: 10.1242/dev.125.14.2723. [DOI] [PubMed] [Google Scholar]
  20. Kingsley D. M. The TGF-beta superfamily: new members, new receptors, and new genetic tests of function in different organisms. Genes Dev. 1994 Jan;8(2):133–146. doi: 10.1101/gad.8.2.133. [DOI] [PubMed] [Google Scholar]
  21. Lyons K. M., Hogan B. L., Robertson E. J. Colocalization of BMP 7 and BMP 2 RNAs suggests that these factors cooperatively mediate tissue interactions during murine development. Mech Dev. 1995 Mar;50(1):71–83. doi: 10.1016/0925-4773(94)00326-i. [DOI] [PubMed] [Google Scholar]
  22. Massagué J., Attisano L., Wrana J. L. The TGF-beta family and its composite receptors. Trends Cell Biol. 1994 May;4(5):172–178. doi: 10.1016/0962-8924(94)90202-x. [DOI] [PubMed] [Google Scholar]
  23. Massagué J. TGF-beta signal transduction. Annu Rev Biochem. 1998;67:753–791. doi: 10.1146/annurev.biochem.67.1.753. [DOI] [PubMed] [Google Scholar]
  24. Massaous J., Hata A. TGF-beta signalling through the Smad pathway. Trends Cell Biol. 1997 May;7(5):187–192. doi: 10.1016/S0962-8924(97)01036-2. [DOI] [PubMed] [Google Scholar]
  25. Mathies L. D., Kerridge S., Scott M. P. Role of the teashirt gene in Drosophila midgut morphogenesis: secreted proteins mediate the action of homeotic genes. Development. 1994 Oct;120(10):2799–2809. doi: 10.1242/dev.120.10.2799. [DOI] [PubMed] [Google Scholar]
  26. Nellen D., Affolter M., Basler K. Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic. Cell. 1994 Jul 29;78(2):225–237. doi: 10.1016/0092-8674(94)90293-3. [DOI] [PubMed] [Google Scholar]
  27. Padgett R. W., Das P., Krishna S. TGF-beta signaling, Smads, and tumor suppressors. Bioessays. 1998 May;20(5):382–390. doi: 10.1002/(SICI)1521-1878(199805)20:5<382::AID-BIES5>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  28. Panganiban G. E., Reuter R., Scott M. P., Hoffmann F. M. A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis. Development. 1990 Dec;110(4):1041–1050. doi: 10.1242/dev.110.4.1041. [DOI] [PubMed] [Google Scholar]
  29. Raftery L. A., Twombly V., Wharton K., Gelbart W. M. Genetic screens to identify elements of the decapentaplegic signaling pathway in Drosophila. Genetics. 1995 Jan;139(1):241–254. doi: 10.1093/genetics/139.1.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Reuter R., Scott M. P. Expression and function of the homoeotic genes Antennapedia and Sex combs reduced in the embryonic midgut of Drosophila. Development. 1990 Jun;109(2):289–303. doi: 10.1242/dev.109.2.289. [DOI] [PubMed] [Google Scholar]
  31. Schlunegger M. P., Grütter M. G. Refined crystal structure of human transforming growth factor beta 2 at 1.95 A resolution. J Mol Biol. 1993 May 20;231(2):445–458. doi: 10.1006/jmbi.1993.1293. [DOI] [PubMed] [Google Scholar]
  32. Segal D., Gelbart W. M. Shortvein, a new component of the decapentaplegic gene complex in Drosophila melanogaster. Genetics. 1985 Jan;109(1):119–143. doi: 10.1093/genetics/109.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sekelsky J. J., Newfeld S. J., Raftery L. A., Chartoff E. H., Gelbart W. M. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics. 1995 Mar;139(3):1347–1358. doi: 10.1093/genetics/139.3.1347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Simin K., Bates E. A., Horner M. A., Letsou A. Genetic analysis of punt, a type II Dpp receptor that functions throughout the Drosophila melanogaster life cycle. Genetics. 1998 Feb;148(2):801–813. doi: 10.1093/genetics/148.2.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Spencer F. A., Hoffmann F. M., Gelbart W. M. Decapentaplegic: a gene complex affecting morphogenesis in Drosophila melanogaster. Cell. 1982 Mar;28(3):451–461. doi: 10.1016/0092-8674(82)90199-4. [DOI] [PubMed] [Google Scholar]
  36. Sporn M. B., Roberts A. B. TGF-beta: problems and prospects. Cell Regul. 1990 Nov;1(12):875–882. doi: 10.1091/mbc.1.12.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sun Y. H., Tsai C. J., Green M. M., Chao J. L., Yu C. T., Jaw T. J., Yeh J. Y., Bolshakov V. N. White as a reporter gene to detect transcriptional silencers specifying position-specific gene expression during Drosophila melanogaster eye development. Genetics. 1995 Nov;141(3):1075–1086. doi: 10.1093/genetics/141.3.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Suzuki A., Kaneko E., Maeda J., Ueno N. Mesoderm induction by BMP-4 and -7 heterodimers. Biochem Biophys Res Commun. 1997 Mar 6;232(1):153–156. doi: 10.1006/bbrc.1997.6219. [DOI] [PubMed] [Google Scholar]
  39. Thüringer F., Cohen S. M., Bienz M. Dissection of an indirect autoregulatory response of a homeotic Drosophila gene. EMBO J. 1993 Jun;12(6):2419–2430. doi: 10.1002/j.1460-2075.1993.tb05896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Tomoyasu Y., Nakamura M., Ueno N. Role of dpp signalling in prepattern formation of the dorsocentral mechanosensory organ in Drosophila melanogaster. Development. 1998 Nov;125(21):4215–4224. doi: 10.1242/dev.125.21.4215. [DOI] [PubMed] [Google Scholar]
  41. Tremml G., Bienz M. Homeotic gene expression in the visceral mesoderm of Drosophila embryos. EMBO J. 1989 Sep;8(9):2677–2685. doi: 10.1002/j.1460-2075.1989.tb08408.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tremml G., Bienz M. Induction of labial expression in the Drosophila endoderm: response elements for dpp signalling and for autoregulation. Development. 1992 Oct;116(2):447–456. doi: 10.1242/dev.116.2.447. [DOI] [PubMed] [Google Scholar]
  43. Twombly V., Blackman R. K., Jin H., Graff J. M., Padgett R. W., Gelbart W. M. The TGF-beta signaling pathway is essential for Drosophila oogenesis. Development. 1996 May;122(5):1555–1565. doi: 10.1242/dev.122.5.1555. [DOI] [PubMed] [Google Scholar]
  44. Wharton K. A., Thomsen G. H., Gelbart W. M. Drosophila 60A gene, another transforming growth factor beta family member, is closely related to human bone morphogenetic proteins. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9214–9218. doi: 10.1073/pnas.88.20.9214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Wisotzkey R. G., Mehra A., Sutherland D. J., Dobens L. L., Liu X., Dohrmann C., Attisano L., Raftery L. A. Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses. Development. 1998 Apr;125(8):1433–1445. doi: 10.1242/dev.125.8.1433. [DOI] [PubMed] [Google Scholar]
  46. Xie T., Finelli A. L., Padgett R. W. The Drosophila saxophone gene: a serine-threonine kinase receptor of the TGF-beta superfamily. Science. 1994 Mar 25;263(5154):1756–1759. doi: 10.1126/science.8134837. [DOI] [PubMed] [Google Scholar]
  47. de Celis J. F. Expression and function of decapentaplegic and thick veins during the differentiation of the veins in the Drosophila wing. Development. 1997 Mar;124(5):1007–1018. doi: 10.1242/dev.124.5.1007. [DOI] [PubMed] [Google Scholar]
  48. ten Dijke P., Miyazono K., Heldin C. H. Signaling via hetero-oligomeric complexes of type I and type II serine/threonine kinase receptors. Curr Opin Cell Biol. 1996 Apr;8(2):139–145. doi: 10.1016/s0955-0674(96)80058-5. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES