Full paper
Sequence, biochemical characterization, and developmental expression of a new member of the TGF-β superfamily in Drosophila melanogaster

https://doi.org/10.1016/0012-1606(92)90188-MGet rights and content

Abstract

More than 20 members of the transforming growth factor-β (TGF-β) superfamily of growth and differentiation factors have been implicated in development. One member of the TGF-β family has been previously reported from Drosophila, the decapentaplegic (dpp) gene which is involved in embryonic dorsal/ventral polarity, embryonic gut formation, and imaginal disk development. Using PCR methods, we have identified a second Drosophila gene in the TGF-β family. It encodes a protein product that is more similar to the TGF-β-related human bone morphogenetic proteins (BMPs) 5, 6, and 7 than it is to the Drosophila dpp gene product. Because of its localization on the polytene chromosome map, we refer to this gene as 60A. Expression of a 60A cDNA in Drosophila S2 cells was used to determine that 60A encodes a preproprotein that is processed to yield secreted amino- and carboxy-terminal polypeptides. The carboxy-terminal peptides are recovered as disulfide-linked homodimers. The 60A transcripts and protein are first detected at the onset of gastrulation, primarily in the mesoderm of the extending germ band. As the germ band retracts, and throughout later stages of embryonic development, the 60A transcript and protein are most readily detected in cells of the developing foregut and hindgut.

References (72)

  • L.S. Mathews et al.

    Expression cloning of an activin receptor, a predicted transmembrane serine kinase

    Cell

    (1991)
  • H.L. Moses et al.

    TGF-β stimulation and inhibition of cell proliferation: New mechanistic insights

    Cell

    (1990)
  • R.W. Pelton et al.

    Differential expression of genes encoding TGFs β1, β2, and β3 during murine palate formation

    Dev. Biol

    (1990)
  • D.C. Rio et al.

    Identification and immunochemical analysis of biologically active Drosophila P element transposase

    Cell

    (1986)
  • D.B. Smith et al.

    Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione-S-transferase

    Gene

    (1988)
  • F.A. Spencer et al.

    Decapentaplegic: A gene complex affecting morphogenesis in Drosophila melanogaster

    Cell

    (1982)
  • G. Thomsen et al.

    Activins are expressed early in Xenopus embryogenesis and can induce axial mesoderm and anterior structures

    Cell

    (1990)
  • D.L. Weeks et al.

    A maternal mRNA localized to the vegetal hemisphere in Xenopus eggs codes for a growth factor related to TGF-β

    Cell

    (1987)
  • M. Ashburner
  • J.E. Badley et al.

    A simple, rapid method for the purification of poly A+ RNA

    BioTechniques

    (1988)
  • M. Bourouis et al.

    Vectors containing a prokaryotic dihydrofolate reductase gene transform Drosophila cells to methotrexate-resistance

    EMBO J

    (1983)
  • T. Bunch et al.

    Characterization and use of the Drosophila metallothionein promoter in cultured Drosophila melanogaster cells

    Nucleic Acids Res

    (1988)
  • J. Campos-Ortega et al.

    The Embryonic Development of Drosophila melanogaster

    (1985)
  • D.R. Cavener

    Comparison of the consensus sequence flanking translational start sites in Drosophila and vertebrates

    Nucleic Acids Res

    (1987)
  • A.J. Celeste et al.

    Identification of transforming growth factor β family members present in bone-inductive protein purified from bovine bone

  • C.L. Deickman et al.

    Assembly of the mitochondrial membrane system

    J. Biol. Chem

    (1985)
  • R. Derynck et al.

    Human transforming growth factor-β cDNA sequence and expression in tumor cell lines

    Nature

    (1985)
  • R. Derynck et al.

    A new type of transforming growth factor-β: TGF-β3

    EMBO J

    (1988)
  • J. Devereaux et al.

    A comprehensive set of sequence analysis programs for the VAX

    Nucleic Acids Res

    (1984)
  • R.G. Forage et al.

    Cloning and sequence analysis of cDNA species coding from the two subunits of inhibin from bovine follicular fluid

  • W.M. Gelbart

    The decapentaplegic gene: A TGF-β homologue controlling pattern formation in Drosophila

    Development (Suppl.)

    (1989)
  • U.I. Heine et al.

    Role of transforming growth factor-β in the development of the mouse embryo

    J. Cell Biol

    (1987)
  • F.M. Hoffmann

    Developmental functions of decapentaplegic, a member of the TGF-β family in Drosophila

  • A.J. Hsueh et al.

    Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis

  • V.F. Irish et al.

    The decapentaplegic gene is required for dorsal-ventral patterning of the Drosophila embryo

    Genes Dev

    (1987)
  • S.B. Jakowlew et al.

    Complementary deoxyribonucleic acid cloning of a messenger ribonucleic acid encoding transforming β4 from chicken embryo chondrocytes

    Mol. Endocrinol

    (1988)
  • Cited by (98)

    • Alternative cleavage of the bone morphogenetic protein (BMP), Gbb, produces ligands with distinct developmental functions and receptor preferences

      2017, Journal of Biological Chemistry
      Citation Excerpt :

      α-GbbN identified a 10-kDa band that matched the expected size of the NH3-NS fragment on Western blottings of the conditioned media. α-GbbCore detected a 28-kDa fragment, which matched the expected size of the NS-S1 cleavage product, and a previously unidentified prodomain fragment (31). Finally, α-GbbC detected the expected Gbb15 ligand secreted into the media (Fig. 1C).

    • BMP morphogen gradients in flies

      2016, Cytokine and Growth Factor Reviews
      Citation Excerpt :

      Bone morphogenetic proteins (BMPs) belong to one of the best-studied family of morphogens. In Drosophila, there are three BMP-type ligands, Decapentaplegic (Dpp), Screw (Scw), and Glass bottom boat (Gbb) [3–5]. Dpp is the Drosophila homolog of vertebrate BMP2/4, Gbb is the homolog of BMP5/6/7/8, and Scw is a distant relative of the BMP5/6/7/8 subclass, with no clear vertebrate ortholog.

    • The Drosophila COMPASS-like Cmi-Trr coactivator complex regulates dpp/BMP signaling in pattern formation

      2013, Developmental Biology
      Citation Excerpt :

      Our chromatin binding data also leaves open the possibility that the Cmi/Trr complex might directly regulate dpp transcription in a subset of cells along the A/P border in the developing wing, likely in collaboration with sequence-specific transcription factors. In the pupal wing, Dpp (BMP2/4) forms a heterodimer with Gbb, a BMP-5/6/7/8 like protein to carry out Tgfβ signaling (Doctor et al., 1992; Khalsa et al., 1998). Dpp and Gbb signal through two Type I Tgfβ receptors, Sax and Tkv and a type II receptor, Punt (Affolter and Basler, 2007).

    • Fast-tracking morphogen diffusion

      2006, Journal of Theoretical Biology
    View all citing articles on Scopus

    This work was supported by grants from the American Cancer Society (NP-612), the NIH (RR06610), and the UW-Madison Graduate School to F.M.H. and by an NCI Cancer Center Core Grant to H. C. Pitot.

    1

    Current address: Dept. of Biological Sciences, Mellon Hall, Duquesne University, Pittsburgh, PA 15282.

    3

    P.D.J. was supported by a fellowship from the NIH.

    2

    F.M.H. is supported by a Faculty Research Award from the ACS.

    View full text