Advertisement
JOURNAL ARTICLES
Migration of the Drosophila primordial midgut cells requires coordination of diverse PS integrin functions
M.D. Martin-Bermudo, I. Alvarez-Garcia, N.H. Brown
Development 1999 126: 5161-5169;

Summary

Cell migration during embryogenesis involves two populations of cells: the migrating cells and the underlying cells that provide the substratum for migration. The formation of the Drosophila larval midgut involves the migration of the primordial midgut cells along a visceral mesoderm substratum. We show that integrin adhesion receptors are required in both populations of cells for normal rates of migration. In the absence of the PS integrins, the visceral mesoderm is disorganised, the primordial midgut cells do not display their normal motile appearance and their migration is delayed by 2 hours. Removing PS integrin function from the visceral mesoderm alone results in visceral mesoderm disorganization, but only causes a modest delay in migration and does not affect the appearance of the migrating cells. Removing PS integrin function from the migrating cells causes as severe a delay in migration as the complete loss of PS integrin function. The functions of PS1 and PS2 are specific in the two tissues, endoderm and mesoderm, since they cannot substitute for each other. In addition there is a partial redundancy in the function of the two PS integrins expressed in the endoderm, PS1 (alphaPS1betaPS) and PS3 (alphaPS3betaPS), since loss of just one alpha subunit in the midgut results in either a modest delay (alphaPS1) or no effect (alphaPS3). We have also examined the roles of small GTPases in promoting migration of the primordial midgut cells. We find that dominant negative (N17) versions of Rac and Cdc42 cause a very similar defect in migration as loss of integrins, while those of Rho and Ras have no effect. Thus integrins are involved in mediating migration by creating an optimal substratum for adhesion, adhering to that substratum and possibly by activating Rac and Cdc42.

Reference

    1. Bauer J. F.,
    2. Varner J.,
    3. Schreiner C.,
    4. Kornberg L.,
    5. Nicholas R.,
    6. Juliano R. L.
    (1993) Functional role of the cytoplasmic domain of the integrin5subunit. J. Cell Biol 122, 209–221
    OpenUrlAbstract/FREE Full Text
    1. Brabant M. C.,
    2. Brower D. L.
    (1993) PS2 Integrin Requirements in Drosophila Embryo and Wing Morphogenesis. Dev. Biol 157, 49–59
    OpenUrlCrossRefPubMedWeb of Science
    1. Brand A. H.,
    2. Perrimon N.
    (1993) Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415
    OpenUrlAbstract
    1. Brower D. L.,
    2. Bunch T. A.,
    3. Mukai L.,
    4. Adamson T. E.,
    5. Wehrli M.,
    6. Lam S.,
    7. Friedlander E.,
    8. Roote C. E.,
    9. Zusman S.
    (1995) Nonequivalent requirements for PS1 and PS2 integrin at cell attachments in Drosophila: genetic analysis of thePS1integrin subunit. Development 121, 1311–1320
    OpenUrlAbstract
    1. Brower D. L.,
    2. Smith R. J.,
    3. Wilcox M.
    (1980) A monoclonal antibody specific for diploid epithelial cells in Drosophila. Nature 285, 403–405
    OpenUrlCrossRefPubMed
    1. Brown N. H.
    (1993) Integrins hold Drosophila together. BioEssays 15, 383–390
    OpenUrlCrossRefPubMedWeb of Science
    1. Brown N. H.
    (1994) Null mutations in thePS2and PSintegrin subunit genes have distinct phenotypes. Development 120, 1221–1231
    OpenUrlAbstract
    1. Bunch T. A.,
    2. Salatino R.,
    3. Engelsgjerd M. C.,
    4. Mukai L.,
    5. West R. F.,
    6. Brower D. L.
    (1992) Characterization of mutant alleles of myospheroid, the gene encoding thesubunit of the Drosophila PS integrins. Genetics 132, 519–528
    OpenUrlAbstract/FREE Full Text
    1. Chou T. B.,
    2. Perrimon N.
    (1992) Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. Genetics 131, 643–653
    OpenUrlAbstract/FREE Full Text
    1. Clark E. A.,
    2. Brugge J. S.
    (1995) Integrins and signal transduction pathways: the road taken. Science 268, 233–239
    OpenUrlAbstract/FREE Full Text
    1. Clark E. A.,
    2. King W. G.,
    3. Brugge J. S.,
    4. Symons M.,
    5. Hynes R. O.
    (1998) Integrin-mediated signals regulated by members of the Rho family of GTPases. J. Cell Biol 142, 573–586
    OpenUrlAbstract/FREE Full Text
    1. Darribere T.,
    2. Guida K.,
    3. Lajarva H.,
    4. Johnson K. E.,
    5. Yamada K. M.,
    6. Thiery J. P.,
    7. Boucaut J. C.
    (1990) In vivo analyses of integrinsubunit function in fibronectin matrix assembly. J. Cell Biol 110, 1813–1823
    OpenUrlAbstract/FREE Full Text
    1. Dunin Borkowski O. M.,
    2. Brown N. H.,
    3. Bate M.
    (1995) Anterior-posterios subdivision and the diversification of the mesoderm in Drosophila. Development 121, 4183–4193
    OpenUrlAbstract
    1. Dunin-Borkowski O. M.,
    2. Brown N. H.
    (1995) Mammalian CD2 is an effective heterologous marker of the cell surface in Drosophila. Dev. Biol 168, 689–693
    OpenUrlCrossRefPubMed
    1. Eaton S.,
    2. Auvinen P.,
    3. Luo L.,
    4. Jan Y. N.,
    5. Simons K.
    (1995) CDC42 and Rac1 control different actin-dependent processes in the Drosophila wing disc epithelium. J. Cell Biol 131, 151–164
    OpenUrlAbstract/FREE Full Text
    1. Farnsworth C. L.,
    2. Feig L. A.
    (1991) Dominant inhibitory mutations in the Mg2+binding site of RasHprevent its activation by GTP. Mol. Cell Biol 11, 4822–4829
    OpenUrlAbstract/FREE Full Text
    1. Fassler R.,
    2. Meyer M.
    (1995) Consequences of lack of1 integrin gene expression in mice. Genes Dev 9, 1896–1908
    OpenUrlAbstract/FREE Full Text
    1. Felsenfeld D. P.,
    2. Choquet D.,
    3. Sheetz M. P.
    (1996) Ligand binding regulates the directed movement of1integrins on fibroblasts. Nature 383, 438–44
    OpenUrlCrossRefPubMed
    1. Georgias C.,
    2. Wasser M.,
    3. Hinz U.
    (1997) A basic-helix-loop-helix protein expressed in precursors of Drosophila longitudinal visceral muscles. Mech. Dev 69, 115–124
    OpenUrlCrossRefPubMedWeb of Science
    1. Greig S.,
    2. Akam M.
    (1993) Homeotic genes autonomously specify one aspect of pattern in the Drosophila mesoderm. Nature 362, 630–632
    OpenUrlCrossRefPubMedWeb of Science
    1. Hanks S. K.,
    2. Polte T. R.
    (1997) Signaling through focal adhesion kinase. BioEssays 19, 137–145
    OpenUrlCrossRefPubMedWeb of Science
    1. Harden N.,
    2. Loh H. Y.,
    3. Chia W.,
    4. Lim L.
    (1995) A dominant inhibitory version of the small GTP-binding protein Rac disrupts cytoskeletal structures and inhibits developmental cell shape changes in Drosophila. Development 121, 903–914
    OpenUrlAbstract
    1. Hidalgo A.,
    2. Urban J.,
    3. Brand A. H.
    (1995) Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS. Development 121, 3703–3712
    OpenUrlAbstract
    1. Hildebrand J. D.,
    2. Taylor J. M.,
    3. Parsons J. T.
    (1996) An SH3 domain-containing GTPase-activating protein for Rho and CDC42 associates with focal adhesion kinase. Mol. Cell Biol 16, 3169–3178
    OpenUrlAbstract/FREE Full Text
    1. Hotchin N. A.,
    2. Hall A.
    (1995) The assembly of integrin adhesion complexes require both extracellular matrix and intracellular Rho/Rac GTPases. J. Cell Biol 131, 1857–1865
    OpenUrlAbstract/FREE Full Text
    1. Huttenlocher A.,
    2. Sandborg R. R.,
    3. Horwitz A. F.
    (1995) Adhesion in cell migration. Curr. Opin. Cell Biol 7, 697–706
    OpenUrlCrossRefPubMedWeb of Science
    1. Hynes R. O.
    (1992) Integrins: versatility, modulation, and signaling in cell adhesion. Cell 69, 11–25
    OpenUrlCrossRefPubMedWeb of Science
    1. Keely P. J.,
    2. Westwick J. K.,
    3. Whitehead I. P.,
    4. Der C. J.,
    5. Parise L. V.
    (1997) Cdc42 and Rac1 induce integrin-mediated cell motility and invasiveness through PI(3)K. Nature 390, 632–635
    OpenUrlCrossRefPubMed
    1. Klinghoffer R. A.,
    2. Sachsenmaier C.,
    3. Cooper J. A.,
    4. Soriano P.
    (1999) Src family kinases are required for integrin but not PDGFR signal transduction. EMBOJ 18, 2459–2471
    OpenUrlAbstract
    1. Lauffenburger D. A.,
    2. Horwitz A. F.
    (1996) Cell Migration: A Physically Integrated Molecular Process. Cell 84, 359–369
    OpenUrlCrossRefPubMedWeb of Science
    1. Lee T.,
    2. Feig L.,
    3. Montell D. J.
    (1996) Two distinct roles for Ras in a developmentally regulated cell migration. Development 122, 409–418
    OpenUrlAbstract
    1. Luo L.,
    2. Liao Y. J.,
    3. Jan L. Y.,
    4. Jan Y. N.
    (1994) Distinct morphogenetic functions of similar small GTPases: Drosophila Drac1 is involved in axonal outgrowth and myoblast fusion. Genes Dev 8, 1787–1802
    OpenUrlAbstract/FREE Full Text
    1. Martin-Bermudo M. D.,
    2. Brown N.H.
    (1999) Uncoupling integrin adhesion and signaling: thePScytoplasmic domain is sufficient to regulate gene expression in the Drosophila embryo. Genes Dev 13, 729–739
    OpenUrlAbstract/FREE Full Text
    1. Martin-Bermudo M. D.,
    2. Brown N. H.
    (1996) Intracellular signals direct integrin localization to sites of function in embryonic muscles. J. Cell. Biol 134, 217–226
    OpenUrlAbstract/FREE Full Text
    1. Martin-Bermudo M. D.,
    2. Dunin-Borkowski O. M.,
    3. Brown N.H.
    (1997) Specificity of PS integrin function during embryogenesis resides in thesubunit extracellular domain. EMBO J 16, 4184–4193
    OpenUrlAbstract/FREE Full Text
    1. Michiels F.,
    2. Habets G. G.,
    3. Stam J. C.,
    4. van der Kammen R. A.,
    5. Gollard J. C.
    (1995) A role for Rac in Tiam 1-induced membrane ruffling and invasion. Nature 375, 338–340
    OpenUrlCrossRefPubMedWeb of Science
    1. Miyamoto S.,
    2. Akiyama S. K.,
    3. Yamada K. M.
    (1995) Synergistic roles for receptor occupancy and aggregation in integrin transmembrane function. Science 267, 883–885
    OpenUrlAbstract/FREE Full Text
    1. Murphy A. M.,
    2. Montell D. J.
    (1996) Cell type-specific roles for Cdc42, Rac, and RhoL in Drosophila oogenesis. J. Cell Biol 133, 617–630
    OpenUrlAbstract/FREE Full Text
    1. Nobes C. D.,
    2. Hall A.
    (1995) Rho, Rac and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62
    OpenUrlCrossRefPubMedWeb of Science
    1. Palecek S. P.,
    2. Loftus J. C.,
    3. Ginsberg M. H.,
    4. Lauffenburger D. A.,
    5. Horwitz A.
    (1997) Integrin-ligand binding properties govern cell migration speed through cell-substratum adhesiveness. Nature 385, 537–540
    OpenUrlCrossRefPubMedWeb of Science
    1. Prokop A.,
    2. Martin-Bermudo M. D.,
    3. Bate M.,
    4. Brown N. H.
    (1998) In Drosophila embryos, the absence of the PS integrins or laminin A affects the extracellular adhesion of hemiadherens and neuromuscular junctions, but not their intracellular assembly. Dev. Biol 196, 58–76
    OpenUrlCrossRefPubMed
    1. Qiu R. G.,
    2. Chen J.,
    3. Kirn D.,
    4. McCormick F.,
    5. Symons M.
    (1995) An essential role for Rac in Ras transformation. Nature 374, 457–459
    OpenUrlCrossRefPubMedWeb of Science
    1. Reuter R.,
    2. Grunewald B.,
    3. Leptin M.
    (1993) A role for mesoderm in endodermal migration and morphogenesis in Drosophila. Development 119, 1135–1145
    OpenUrlAbstract
    1. Roote C. E.,
    2. Zusman S.
    (1995) Functions for PS integrins in tissue adhesion, migration, and shape changes during early embryonic development in Drosophila. Dev. Biol 169, 322–336
    OpenUrlCrossRefPubMedWeb of Science
    1. Stark K. A.,
    2. Yee G. H.,
    3. Roote C. E.,
    4. Williams E. L.,
    5. Zusman S.,
    6. Hynes R. O.
    (1997) A novelintegrin subunit associates with PS and functions in tissue morphogenesis and movement during Drosophila development. Development 124, 4583–4594
    OpenUrlAbstract
    1. Strutt D. I.,
    2. Weber U.,
    3. Mlodzik M.
    (1997) The role of RhoA in tissue polarity and Frizzled signalling. Nature 387, 292–295
    OpenUrlCrossRefPubMedWeb of Science
    1. Takaishi K.,
    2. Kikuchi A.,
    3. Kuroda S.,
    4. Kotani K.,
    5. Sasaki T.,
    6. Takai Y.
    (1993) Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility. Mol. Cell Biol 13, 72–79
    OpenUrlAbstract/FREE Full Text
    1. Tepass U.,
    2. Hartenstein V.
    (1994) Epithelium formation in the Drosophila midgut depends on the interaction of endoderm and mesoderm. Development 120, 579–590
    OpenUrlAbstract
    1. Yamada K. M.,
    2. Geiger B.
    (1997) Molecular interactions in cell adhesion complexes. Curr. Biol 9, 76–85
    1. Zipkin I. D.,
    2. Kindt R. M.,
    3. Kenyon C. J.
    (1997) Role of a new Rho family member in cell migration and axon guidance in C. elegans. Cell 90, 883–894
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Migration of the Drosophila primordial midgut cells requires coordination of diverse PS integrin functions
M.D. Martin-Bermudo, I. Alvarez-Garcia, N.H. Brown
Development 1999 126: 5161-5169;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

An interview with Swathi Arur

Swathi Arur joined the team at Development as an Academic Editor in 2020. Her lab uses multidisciplinary approaches to understand female germline development and fertility. We met with her over Zoom to hear more about her life, her career and her love for C. elegans.

Jim Wells and Hanna Mikkola join our team of Editors

We are pleased to welcome James (Jim) Wells and Hanna Mikkola to our team of Editors. Jim joins us a new Academic Editor, taking over from Gordan Keller, and Hanna joins our team of Associate Editors. Find out more about their research interests and areas of expertise.

New funding scheme supports sustainable events

As part of our Sustainable Conferencing Initiative, we are pleased to announce funding for organisers that seek to reduce the environmental footprint of their event. The next deadline to apply for a Scientific Meeting grant is 26 March 2021.

Read & Publish participation continues to grow

“I’d heard of Read & Publish deals and knew that many universities, including mine, had signed up to them but I had not previously understood the benefits that these deals bring to authors who work at those universities.”

Professor Sally Lowell (University of Edinburgh) shares her experience of publishing Open Access as part of our growing Read & Publish initiative. We now have over 150 institutions in 15 countries and four library consortia taking part – find out more and view our full list of participating institutions.

Upcoming special issues

Imaging Development, Stem Cells and Regeneration
Submission deadline: 30 March 2021
Publication: mid-2021

The Immune System in Development and Regeneration
Guest editors: Florent Ginhoux and Paul Martin
Submission deadline: 1 September 2021
Publication: Spring 2022

Both special issues welcome Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

Development presents...

Our successful webinar series continues into 2021, with early-career researchers presenting their papers and a chance to virtually network with the developmental biology community afterwards. Here, Michèle Romanos talks about her new preprint, which mixes experimentation in quail embryos and computational modelling to understand how heterogeneity in a tissue influences cell rate.

Save your spot at our next session:

10 March
Time: 9:00 (GMT)
Chaired by: Thomas Lecuit

Join our mailing list to receive news and updates on the series.