Skip to main content
SpringerLink
Log in

The role of LamininB2 (LanB2) during mesoderm differentiation in Drosophila

  • Research Article
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

In Drosophila, four genes encode for laminin subunits and the formation of two laminin heterotrimers has been postulated. We report the identification of mutations in the Drosophila LamininB2 (LanB2) gene that encodes for the only laminin γ subunit and is found in both heterotrimers. We describe their effects on embryogenesis, in particular the differentiation of visceral tissues with respect to the ECM. Analysis of mesoderm endoderm interaction indicates disrupted basement membranes and defective endoderm migration, which finally interferes with visceral myotube stretching. Extracellular deposition of laminin is blocked due to the loss of the LanB2 subunit, resulting in an abnormal distribution of ECM components. Our data, concerning the different function of both trimers during organogenesis, suggest that these trimers might act in a cumulative way and probably at multiple steps during ECM assembly. We also observed genetic interactions with kon-tiki and thrombospondin, indicating a role for laminin during muscle attachment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Azpiazu N, Frasch M (1993) tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila. Genes Dev 7(7B):1325–1340

    Article  PubMed  CAS  Google Scholar 

  2. Bate M (1993) The mesoderm and its derivatives. In: Bate M, Martinez Arias A (eds) The development of Drosophila melanogaster, vol II. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  3. Campos-Ortega JA, Hartenstein V (1985) The embryonic development of Drosophila melanogaster, 1st edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  4. Klapper R, Stute C, Schomaker O, Strasser T, Janning W, Renkawitz-Pohl R, Holz A (2002) The formation of syncytia within the visceral musculature of the Drosophila midgut is dependent on duf, sns and mbc. Mech Dev 110(1–2):85–96

    Article  PubMed  CAS  Google Scholar 

  5. Kusch T, Reuter R (1999) Functions for Drosophila brachyenteron and forkhead in mesoderm specification and cell signalling. Development 126(18):3991–4003

    PubMed  CAS  Google Scholar 

  6. Poulson DF (1950) Histogenesis, organogenesis, and differentiation in the embryo of Drosophila melanogaster Meigen. In: Demerec M (ed) Biology of Drosophila. Hafner, New York, pp 168–274 (reprinted 1965)

    Google Scholar 

  7. Reuter R, Grunewald B, Leptin M (1993) A role for the mesoderm in endodermal migration and morphogenesis in Drosophila. Development 119(4):1135–1145

    PubMed  CAS  Google Scholar 

  8. San Martin B, Ruiz-Gomez M, Landgraf M, Bate M (2001) A distinct set of founders and fusion-competent myoblasts make visceral muscles in the Drosophila embryo. Development 128(17):3331–3338

    CAS  Google Scholar 

  9. Schröter RH, Buttgereit D, Beck L, Holz A, Renkawitz-Pohl R (2006) Blown fuse regulates stretching and outgrowth but not myoblast fusion of the circular visceral muscles in Drosophila. Differentiation 74(9–10):608–621

    Article  PubMed  Google Scholar 

  10. Tepass U, Hartenstein V (1994) Epithelium formation in the Drosophila midgut depends on the interaction of endoderm and mesoderm. Development 120(3):579–590

    PubMed  CAS  Google Scholar 

  11. Zaffran S, Küchler A, Lee HH, Frasch M (2001) biniou (FoxF), a central component in a regulatory network controlling visceral mesoderm development and midgut morphogenesis in Drosophila. Genes Dev 15(21):2900–2915

    PubMed  CAS  Google Scholar 

  12. Martin-Bermudo MD, Alvarez-Garcia I, Brown NH (1999) Migration of the Drosophila primordial midgut cells requires coordination of diverse PS integrin functions. Development 126(22):5161–5169

    PubMed  CAS  Google Scholar 

  13. Hynes RO (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69(1):11–25

    Article  PubMed  CAS  Google Scholar 

  14. Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110(6):673–687

    Article  PubMed  CAS  Google Scholar 

  15. Aumailley M, Smyth N (1998) The role of laminins in basement membrane function. J Anat 193(1):1–21

    Article  PubMed  CAS  Google Scholar 

  16. Durbeej M (2009) Laminins. Cell Tissue Res 339(1):259–268

    Article  PubMed  Google Scholar 

  17. Timpl R (1996) Macromolecular organization of basement membranes. Curr Opin Cell Biol 8(5):618–624

    Article  PubMed  CAS  Google Scholar 

  18. Martin D, Zusman S, Li X, Williams EL, Khare N, DaRocha S, Chiquet-Ehrismann R, Baumgartner S (1999) wing blister, A new Drosophila Laminin α chain required for cell adhesion and migration during embryonic and imaginal development. J Cell Biol 145(1):191–201. doi:10.1083/jcb.145.1.191

    Article  PubMed  CAS  Google Scholar 

  19. Montell DJ, Goodman CS (1988) Drosophila substrate adhesion molecule: sequence of laminin B1 chain reveals domains of homology with mouse. Cell 53(3):463–473

    Article  PubMed  CAS  Google Scholar 

  20. Montell DJ, Goodman CS (1989) Drosophila Laminin: sequence of B2 subunit and expression of all three subunits during embryogenesis. J Cell Biol 109(5):2441–2453. doi:10.1083/jcb.109.5.2441

    Article  PubMed  CAS  Google Scholar 

  21. Timpl R, Brown JC (1996) Supramolecular assembly of basement membranes. BioEssays 18(2):123–132

    Article  PubMed  CAS  Google Scholar 

  22. Henchcliffe C, Garcia-Alonso L, Tang J, Goodman CS (1993) Genetic analysis of laminin A reveals diverse functions during morphogenesis in Drosophila. Development 118(2):325–337

    PubMed  CAS  Google Scholar 

  23. Prokop A, Martin-Bermudo MD, Bate M, Brown NH (1998) Absence of PS integrins or laminin A affects extracellular adhesion, but not intracellular assembly, of hemiadherens and neuromuscular junctions in Drosophila embryos. Dev Biol 196(1):58–76

    Article  PubMed  CAS  Google Scholar 

  24. Yarnitzky T, Volk T (1995) Laminin is required for heart, somatic muscles, and gut development in the Drosophila embryo. Dev Biol 169(2):609–618

    Article  PubMed  CAS  Google Scholar 

  25. Urbano JM, Torgler CN, Molnar C, Tepass U, Lopez-Varea A, Brown NH, de Celis JF, Martin-Bermudo MD (2009) Drosophila laminins act as key regulators of basement membrane assembly and morphogenesis. Development 136(24):4165–4176. doi:10.1242/dev.044263

    Article  PubMed  CAS  Google Scholar 

  26. Hummel T, Schimmelpfeng K, Klämbt C (1999) Commissure formation in the embryonic CNS of Drosophila. Development 126(4):771–779

    PubMed  CAS  Google Scholar 

  27. Hummel T, Schimmelpfeng K, Klämbt C (1999) Commissure formation in the embryonic CNS of Drosophila: I. identification of the required gene functions. Dev Biol 209(2):381–398

    Article  PubMed  CAS  Google Scholar 

  28. Wolfstetter G, Shirinian M, Stute C, Grabbe C, Hummel T, Baumgartner S, Palmer RH, Holz A (2009) Fusion of circular and longitudinal muscles in Drosophila is independent of the endoderm but further visceral muscle differentiation requires a close contact between mesoderm and endoderm. Mech Dev 126(8–9):721–736

    Article  PubMed  CAS  Google Scholar 

  29. Leicht BG, Bonner JJ (1988) Genetic analysis of chromosomal region 67A-D of Drosophila melanogaster. Genetics 119(3):579–593

    PubMed  CAS  Google Scholar 

  30. Ashburner M, Tsubota S, Woodruff RC (1982) The genetics of a small chromosome region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. Genetics 102:401–420

    PubMed  CAS  Google Scholar 

  31. Woodruff RC, Ashburner M (1979) The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. Genetics 92:133–149

    PubMed  CAS  Google Scholar 

  32. Sellin J, Albrecht S, Kölsch V, Paululat A (2006) Dynamics of heart differentiation, visualized utilizing heart enhancer elements of the Drosophila melanogaster bHLH transcription factor Hand. Gene Expr Patterns 6(4):360–375

    Article  PubMed  CAS  Google Scholar 

  33. Häcker U, Kaufmann E, Hartmann C, Jürgens G, Knochel W, Jäckle H (1995) The Drosophila fork head domain protein crocodile is required for the establishment of head structures. Embo J 14(21):5306–5317

    PubMed  Google Scholar 

  34. Morin X, Daneman R, Zavortink M, Chia W (2001) A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila. Proc Natl Acad Sci USA 98(26):15050–15055

    Article  PubMed  CAS  Google Scholar 

  35. Wodarz A, Hinz U, Engelbert M, Knust E (1995) Expression of crumbs confers apical character on plasma membrane domains of ectodermal epithelia of Drosophila. Cell 82(1):67–76

    Article  PubMed  CAS  Google Scholar 

  36. Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M, Gasser B, Kinsey K, Oppel S, Scheiblauer S, Couto A, Marra V, Keleman K, Dickson BJ (2007) A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448(7150):151–156

    Article  PubMed  CAS  Google Scholar 

  37. Chihara T, Kato K, Taniguchi M, Ng J, Hayashi S (2003) Rac promotes epithelial cell rearrangement during tracheal tubulogenesis in Drosophila. Development 130(7):1419–1428. doi:10.1242/dev.00361

    Article  PubMed  CAS  Google Scholar 

  38. Chanana B, Graf R, Koledachkina T, Pflanz R, Vorbrüggen G (2007) αPS2 integrin-mediated muscle attachment in Drosophila requires the ECM protein thrombospondin. Mech Dev 124(6):463–475

    Article  PubMed  CAS  Google Scholar 

  39. Estrada B, Gisselbrecht SS, Michelson AM (2007) The transmembrane protein Perdido interacts with grip and integrins to mediate myotube projection and attachment in the Drosophila embryo. Development 134(24):4469–4478

    Article  PubMed  CAS  Google Scholar 

  40. Schnorrer F, Kalchhauser I, Dickson BJ (2007) The transmembrane protein Kon-tiki couples to Dgrip to mediate myotube targeting in Drosophila. Developmental Cell 12(5):751–766

    Article  PubMed  CAS  Google Scholar 

  41. Stute C, Schimmelpfeng K, Renkawitz-Pohl R, Palmer RH, Holz A (2004) Myoblast determination in the somatic and visceral mesoderm depends on Notch signalling as well as on milliways (mili Alk) as receptor for Jeb signalling. Development 131(4):743–754

    Article  PubMed  CAS  Google Scholar 

  42. Schneider M, Baumgartner S (2008) Differential expression of Dystroglycan-spliceforms with and without the mucin-like domain during Drosophila embryogenesis. Fly 2(1):29–35

    PubMed  Google Scholar 

  43. Oda H, Uemura T, Harada Y, Iwai Y, Takeichi M (1994) A Drosophila homolog of cadherin associated with armadillo and essential for embryonic cell-cell adhesion. Dev Biol 165(2):716–726

    Article  PubMed  CAS  Google Scholar 

  44. Grenningloh G, Rehm EJ, Goodman CS (1991) Genetic analysis of growth cone guidance in Drosophila: fasciclin II functions as a neuronal recognition molecule. Cell 67(1):45–57

    Article  PubMed  CAS  Google Scholar 

  45. Patel NH, Snow PM, Goodman CS (1987) Characterization and cloning of fasciclin III: a glycoprotein expressed on a subset of neurons and axon pathways in Drosophila. Cell 48(6):975–988

    Article  PubMed  CAS  Google Scholar 

  46. Sokol NS, Cooley L (1999) Drosophila Filamin encoded by the cheerio locus is a component of ovarian ring canals. Curr Biol 9(21):1221–1230

    Article  PubMed  CAS  Google Scholar 

  47. Kusche-Gullberg M, Garrison K, MacKrell AJ, Fessler LI, Fessler JH (1992) Laminin A chain: expression during Drosophila development and genomic sequence. EMBO J 11:4519–4527

    PubMed  CAS  Google Scholar 

  48. Hortsch M, Olson A, Fishman S, Soneral SN, Marikar Y, Dong R, Jacobs JR (1998) The expression of MDP-1, a component of Drosophila embryonic basement membranes, is modulated by apoptotic cell death. Int J Dev Biol 42(1):33–42

    PubMed  CAS  Google Scholar 

  49. Chartier A, Zaffran S, Astier M, Semeriva M, Gratecos D (2002) Pericardin, a Drosophila type IV collagen-like protein is involved in the morphogenesis and maintenance of the heart epithelium during dorsal ectoderm closure. Development 129(13):3241–3253

    PubMed  CAS  Google Scholar 

  50. Martinek N, Shahab J, Saathoff M, Ringuette M (2008) Haemocyte-derived SPARC is required for collagen-IV-dependent stability of basal laminae in Drosophila embryos. J Cell Sci 121(10):1671–1680

    Article  PubMed  CAS  Google Scholar 

  51. Leiss D, Hinz U, Gasch A, Mertz R, Renkawitz-Pohl R (1988) Beta 3 tubulin expression characterizes the differentiating mesodermal germ layer during Drosophila embryogenesis. Development 104(4):525–531

    PubMed  CAS  Google Scholar 

  52. Beck K, Hunter I, Engel J (1990) Structure and function of laminin: anatomy of a multidomain glycoprotein. FASEB J 4(2):148–160

    PubMed  CAS  Google Scholar 

  53. Riechmann V, Rehorn KP, Reuter R, Leptin M (1998) The genetic control of the distinction between fat body and gonadal mesoderm in Drosophila. Development 125(4):713–723

    PubMed  CAS  Google Scholar 

  54. Holz A, Bossinger B, Strasser T, Janning W, Klapper R (2003) The two origins of hemocytes in Drosophila. Development 130(20):4955–4962

    Article  PubMed  CAS  Google Scholar 

  55. Kumagai C, Kadowaki T, Kitagawa Y (1997) Disulfide-bonding between Drosophila laminin and chains is essential for chain to form trimer. FEBS Letters 412(1):211–216

    Article  PubMed  CAS  Google Scholar 

  56. Firth LC, Baker NE (2007) Spitz from the retina regulates genes transcribed in the second mitotic wave, peripodial epithelium, glia and plasmatocytes of the Drosophila eye imaginal disc. Dev Biol 307(2):521–538

    Article  PubMed  CAS  Google Scholar 

  57. Mayer U, Nischt R, Poschl E, Mann K, Fukuda K, Gerl M, Yamada Y, Timpl R (1993) A single EGF-like motif of laminin is responsible for high affinity nidogen binding. EMBO J 12(5):1879–1885

    PubMed  CAS  Google Scholar 

  58. Hamill KJ, Kligys K, Hopkinson SB, Jones JCR (2009) Laminin deposition in the extracellular matrix: a complex picture emerges. J Cell Sci 122(24):4409–4417. doi:10.1242/jcs.041095

    Article  PubMed  CAS  Google Scholar 

  59. Yurchenco PD, Amenta PS, Patton BL (2004) Basement membrane assembly, stability and activities observed through a developmental lens. Matrix Biol 22(7):521–538

    Article  PubMed  CAS  Google Scholar 

  60. Martinek N, Zou R, Berg M, Sodek J, Ringuette M (2002) Evolutionary conservation and association of SPARC with the basal lamina in Drosophila. Dev Genes Evol 212(3):124–133

    Article  PubMed  CAS  Google Scholar 

  61. Goldstein MA, Burdette WJ (1971) Striated visceral muscle of Drosophila melanogaster. J Morphol 134(3):315–334

    Article  PubMed  CAS  Google Scholar 

  62. Chi HC, Hui CF (1988) cDNA and amino acid sequences of Drosophila laminin B2 chain. Nucleic Acids Res 16:7205–7206

    Article  PubMed  CAS  Google Scholar 

  63. Chi HC, Hui CF (1989) Primary structure of the Drosophila laminin B2 chain and comparison with human, mouse, and Drosophila laminin B1 and B2 chains. J Biol Chem 264(3):1543–1550

    PubMed  CAS  Google Scholar 

  64. Devenport D, Brown NH (2004) Morphogenesis in the absence of integrins: mutation of both Drosophila beta subunits prevents midgut migration. Development 131(21):5405–5415

    Article  PubMed  CAS  Google Scholar 

  65. Roote CE, Zusman S (1995) Functions for PS integrins in tissue adhesion, migration, and shape changes during early embryonic development in Drosophila. Dev Biol 169(1):322–336

    Article  PubMed  CAS  Google Scholar 

  66. Luckenbill-Edds L (1997) Laminin and the mechanism of neuronal outgrowth. Brain Res Rev 23(1–2):1–27

    Article  PubMed  CAS  Google Scholar 

  67. Burg MA, Tillet E, Timpl R, Stallcup WB (1996) Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix molecules. J Biol Chem 271(42):26110–26116. doi:10.1074/jbc.271.42.26110

    Article  PubMed  CAS  Google Scholar 

  68. Tillet E, Gential B, Garrone R, Stallcup WB (2002) NG2 proteoglycan mediates β1 integrin-independent cell adhesion and spreading on collagen VI. J Cell Biochem 86(4):726–736

    Article  PubMed  CAS  Google Scholar 

  69. Gotwals PJ, Fessler LI, Wehrli M, Hynes RO (1994) Drosophila PS1 integrin is a laminin receptor and differs in ligand specificity from PS2. Proc Natl Acad Sci USA 91(24):11447–11451

    Article  PubMed  CAS  Google Scholar 

  70. Mumby SM, Raugi GJ, Bornstein P (1984) Interactions of thrombospondin with extracellular matrix proteins: selective binding to type V collagen. J Cell Biol 98(2):646–652. doi:10.1083/jcb.98.2.646

    Article  PubMed  CAS  Google Scholar 

  71. Subramanian A, Wayburn B, Bunch T, Volk T (2007) Thrombospondin-mediated adhesion is essential for the formation of the myotendinous junction in Drosophila. Development 134(7):1269–1278

    Article  PubMed  CAS  Google Scholar 

  72. Sasaki T, Fässler R, Hohenester E (2004) Laminin. J Cell Biol 164(7):959–963. doi:10.1083/jcb.200401058

    Article  PubMed  CAS  Google Scholar 

  73. Yurchenco PD, Cheng YS, Colognato H (1992) Laminin forms an independent network in basement membranes. J Cell Biol 117(5):1119–1133. doi:10.1083/jcb.117.5.1119

    Article  PubMed  CAS  Google Scholar 

  74. Li S, Harrison D, Carbonetto S, Fässler R, Smyth N, Edgar D, Yurchenco PD (2002) Matrix assembly, regulation, and survival functions of laminin and its receptors in embryonic stem cell differentiation. J Cell Biol 157(7):1279–1290. doi:10.1083/jcb.200203073

    Article  PubMed  CAS  Google Scholar 

  75. Schöck F, Perrimon N (2003) Retraction of the Drosophila germ band requires cell-matrix interaction. Genes Dev 17(5):597–602

    Article  PubMed  Google Scholar 

  76. Colognato H, Winkelmann DA, Yurchenco PD (1999) Laminin polymerization induces a receptor-cytoskeleton network. J Cell Biol 145(3):619–631. doi:10.1083/jcb.145.3.619

    Article  PubMed  CAS  Google Scholar 

  77. Colognato H, Yurchenco PD (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218(2):213–234

    Article  PubMed  CAS  Google Scholar 

  78. Schneider M, Khalil AA, Poulton J, Castillejo-Lopez C, Egger-Adam D, Wodarz A, Deng WM, Baumgartner S (2006) Perlecan and dystroglycan act at the basal side of the Drosophila follicular epithelium to maintain epithelial organization. Development 133(19):3805–3815

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We are grateful to Christian Klämbt for sharing fly stock collections and Susanne Önel for critical reading of the manuscript. We thank Stefan Baumgartner, BDGP, the Bloomington Stock Center, Lynn Cooley, the DGRC, the Developmental Studies Hybridoma Bank, Liselotte Fessler, Michael Hortsch, Elisabeth Knust, Achim Paululat, Renate Renkawitz-Pohl, Rolf Reuter, Maurice Ringuette, John Roote, Martina Schneider, the VDRC, Talila Volk, and Gerd Vorbrüggen for sending materials and fly stocks. This work was supported by the Deutsche Forschungsgemeinschaft to Anne Holz (Ho-2559/3-2 and 3-3).

Author information

Authors and Affiliations

  1. Institut für Allgemeine und Spezielle Zoologie, Justus-Liebig-Universität Giessen, Stephanstrasse 24, 35390, Giessen, Germany

    Georg Wolfstetter & Anne Holz

Authors
  1. Georg Wolfstetter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne Holz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anne Holz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wolfstetter, G., Holz, A. The role of LamininB2 (LanB2) during mesoderm differentiation in Drosophila . Cell. Mol. Life Sci. 69, 267–282 (2012). https://doi.org/10.1007/s00018-011-0652-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-011-0652-3

Keywords

Search

Navigation