Advertisement
JOURNAL ARTICLES
The type I serine/threonine kinase receptor Alk8/Lost-a-fin is required for Bmp2b/7 signal transduction during dorsoventral patterning of the zebrafish embryo
H. Bauer, Z. Lele, G.J. Rauch, R. Geisler, M. Hammerschmidt
Development 2001 128: 849-858;

Summary

Ventral specification of mesoderm and ectoderm depends on signaling by members of the bone morphogenetic protein (Bmp) family. Bmp signals are transmitted by a complex of type I and type II serine/threonine kinase transmembrane receptors. Here, we show that Alk8, a novel member of the Alk1 subgroup of type I receptors, is disrupted in zebrafish lost-a-fin (laf) mutants. Two alk8/laf null alleles are described. In laf(tm110), a conserved extracellular cysteine residue is replaced by an arginine, while in laf(m100), Alk8 is prematurely terminated directly after the transmembrane domain. The zygotic effect of both mutations leads to dorsalization of intermediate strength. A much stronger dorsalization, similar to that of bmp2b/swirl and bmp7/snailhouse mutants, however, is obtained by inhibiting both maternally and zygotically supplied alk8 gene products with morpholino antisense oligonucleotides. The phenotype of laf mutants and alk8 morphants can be rescued by injected mRNA encoding Alk8 or the Bmp-regulated transcription factor Smad5, but not by mRNA encoding Bmp2b or Bmp7. Conversely, injected mRNA encoding a constitutively active version of Alk8 can rescue the strong dorsalization of bmp2b/swirl and bmp7/snailhouse mutants, whereas smad5/somitabun mutant embryos do not respond. Altogether, the data suggest that Alk8 acts as a Bmp2b/7 receptor upstream of Smad5.

Reference

    1. Armes N. A.,
    2. Smith J. C.
    (1997) The ALK-2 and ALK-4 activin receptors transduce distinct mesoderm-inducing signals during early Xenopus development but do not co-operate to establish thresholds. Development 124, 3797–3084
    OpenUrlAbstract
    1. Attisano L.,
    2. Carcamo J.,
    3. Ventura F.,
    4. Weis F. M.,
    5. Massague J.,
    6. Wrana J. L.
    (1993) Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors. Cell 75, 671–680
    OpenUrlCrossRefPubMedWeb of Science
    1. Bassing C.H.,
    2. Yingling J.M.,
    3. Howe D.J.,
    4. Wang T.,
    5. He W.W.,
    6. Gustafson M.L.,
    7. Shah P.,
    8. Donahoe P.K.,
    9. Wang X.-F.
    (1994) A transforming growth factortype I receptor that signals to activate gene expression. Science 263, 87–89
    OpenUrlAbstract/FREE Full Text
    1. Bauer H.,
    2. Meier A.,
    3. Hild M.,
    4. Stachel S.,
    5. Economides A.,
    6. Hazelett D.,
    7. Harland R. M.,
    8. Hammerschmidt M.
    (1998) Follistatin and Noggin are excluded from the zebrafish organizer. Dev. Biol 204, 488–507
    OpenUrlCrossRefPubMedWeb of Science
    1. Blader P.,
    2. Rastegar S.,
    3. Fischer N.,
    4. Strähle U.
    (1997) Cleavage of the BMP-4 antagonist Chordin by zebrafish Tolloid. Science 278, 1937–1940
    OpenUrlAbstract/FREE Full Text
    1. Brummel T. J.,
    2. Twombly V.,
    3. Marques G.,
    4. Wrana J. L.,
    5. Newfeld S. J.,
    6. Attisano L.,
    7. Massague J.,
    8. O'Connor M. B.,
    9. Gelbart W. M.
    (1994) Characterization and relationship of Dpp receptors encoded by the saxophone and thick veins genes in Drosophila. Cell 78, 251–261
    OpenUrlCrossRefPubMedWeb of Science
    1. Chen Y.,
    2. Riese M. J.,
    3. Killinger M. A.,
    4. Hoffmann F. M.
    (1998) A genetic screen for modifiers of Drosophiladecapentaplegic signaling identifies mutations in punt, mothers against dpp and the BMP-7 homologue, 60A. Development 125, 1759–1768
    OpenUrlAbstract
    1. Chen Y.-G.,
    2. Hata A.,
    3. Lo R. S.,
    4. Wotton D.,
    5. Shi Y.,
    6. Pavletich N.,
    7. Massague J.
    (1998) Determinants of specificity in TGF-signal transduction. Genes Dev 12, 2144–2152
    OpenUrlAbstract/FREE Full Text
    1. Chen Y. G.,
    2. Massague J.
    (1999) Smad1 recognition and activation by the ALK1 group of transforming growth factor-family receptors. J. Biol. Chem 274, 3672–3677
    OpenUrlAbstract/FREE Full Text
    1. Connors S. A.,
    2. Trout J.,
    3. Ekker M.,
    4. Mullins M. C.
    (1999) The role of tolloid / minifin in dorsoventral pattern formation of the zebrafish embryo. Development 126, 3119–3130
    OpenUrlAbstract
    1. Czaplinski K.,
    2. Ruiz-Echevarria M. J.,
    3. González C. I.,
    4. Peltz S. W.
    (1999) Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover. BioEssays 21, 685–696
    OpenUrlCrossRefPubMedWeb of Science
    1. Dale L.,
    2. Howes G.,
    3. Price B. M. J.,
    4. Smith J. C.
    (1992) Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. Development 115, 573–585
    OpenUrlAbstract
    1. Dick A.,
    2. Hild M.,
    3. Bauer H.,
    4. Imai Y.,
    5. Maifeld H.,
    6. Schier A.,
    7. Talbot W.,
    8. Bouwmeester T.,
    9. Hammerschmidt M.
    (2000) Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development 127, 343–354
    OpenUrlAbstract
    1. Ebner R.,
    2. Chen R. H.,
    3. Lawler S.,
    4. Zioncheck T.,
    5. Derynck R.
    (1993) Determination of type I receptor specificity by the type II receptors for TGF-beta or activin. Science 262, 900–902
    OpenUrlAbstract/FREE Full Text
    1. Geisler R.,
    2. Rauch G.-J.,
    3. Baier H.,
    4. van Bebber F.,
    5. Broβ L.,
    6. Davis R. W.,
    7. Dekens M.,
    8. Finger K.,
    9. Fricke C.,
    10. Gates M. A.,
    11. et al.
    (1999) A radiation hybrid map of the zebrafish genome. Nat. Genet 23, 86–89
    OpenUrlCrossRefPubMedWeb of Science
    1. Graff J. M.,
    2. Thies R. S.,
    3. Song J. J.,
    4. Celeste A. J.,
    5. Melton D. A.
    (1994) Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell 79, 169–179
    OpenUrlCrossRefPubMedWeb of Science
    1. Haerry T. E.,
    2. Khalsa O.,
    3. O'Connor M. B.,
    4. Wharton K. A.
    (1998) Synergistic signaling by two BMP ligands through the SAX and TKV receptors controls wing growth and patterning in Drosophila. Development 125, 3977–3987
    OpenUrlAbstract
    1. Hammerschmidt M.,
    2. Pelegri F.,
    3. Mullins M. C.,
    4. Kane D. A.,
    5. van Eeden F. J. M.,
    6. Granato M.,
    7. Brand M.,
    8. Furutani-Seiki M.,
    9. Haffter P.,
    10. Heisenberg C.-P.,
    11. et al.
    (1996) dino and mercedes, two genes regulating dorsal development in the zebrafish embryo. Development 123, 95–102
    OpenUrlAbstract/FREE Full Text
    1. Hammerschmidt M.,
    2. Serbedzija G. N.,
    3. McMahon A. P.
    (1996) Genetic analysis of dorsoventral pattern formation in the zebrafish: Requirement of a BMP-like ventralizing activity and its dorsal repressor. Genes Dev 10, 2452–2461
    OpenUrlAbstract/FREE Full Text
    1. Hammerschmidt M.,
    2. Blader P.,
    3. Strähle U.
    (1999) Strategies to perturb zebrafish development. Meth. Cell Biol 59, 87–115
    OpenUrlPubMed
    1. Hawley S. H. B.,
    2. Wunnenberg-Stapleton K.,
    3. Hashimoto C.,
    4. Laurent M. N.,
    5. Watabe T.,
    6. Blumberg B. W.,
    7. Cho K. W. Y.
    (1995) Disruption of BMP signals in embryonic Xenopus ectoderm leads to direct neural induction. Genes Dev 9, 2923–2935
    OpenUrlAbstract/FREE Full Text
    1. Heasman J.,
    2. Kofron M.,
    3. Wylie C.
    (2000) -catenin signaling activity dissected in early Xenopus embryos: a novel antisense approach. Dev. Biol 222, 124–134
    OpenUrlCrossRefPubMedWeb of Science
    1. Hild M.,
    2. Dick A.,
    3. Rauch J. G.,
    4. Meier A.,
    5. Bouwmeester T.,
    6. Haffter P.,
    7. Hammerschmidt M.
    (1999) The smad5 mutation somitabun blocks Bmp2b signaling during early dorsoventral patterning of the zebrafish embryo. Development 126, 2149–2159
    OpenUrlAbstract
    1. Hogan B. L. M.
    (1996) Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 10, 1580–1594
    OpenUrlFREE Full Text
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Lapan P. M.,
    4. Wright W. V. E.,
    5. Hogan B. L. M.
    (1992) DVR-4 (bone morphogenetic protein-4) as a posterior ventralizing factor in Xenopus mesoderm induction. Development 115, 639–647
    OpenUrlAbstract
    1. Khalsa O.,
    2. Yoon J. W.,
    3. Torres-Schumann S.,
    4. Wharton K. A.
    (1998) TGF/BMP superfamily members, Gbb-60A and Dpp, cooperate to provide pattern information and establish cell identity in the Drosophila wing. Development 125, 2723–2734
    OpenUrlAbstract
    1. Kishimoto Y.,
    2. Lee K.-H.,
    3. Zon L.,
    4. Hammerschmidt M.,
    5. Schulte-Merker S.
    (1997) The molecular nature of swirl: BMP2 function is essential during early dorsoventral patterning. Development 124, 4457–4466
    OpenUrlAbstract
    1. Knapik E. W.,
    2. Goodman A.,
    3. Ekker M.,
    4. Chevrette M.,
    5. Delgado J.,
    6. Neuhauss S.,
    7. Shimoda N.,
    8. Driever W.,
    9. Fishman M. C.,
    10. Jacob H. J.
    (1998) A microsatellite genetic linkage map for zebrafish (Danio rerio). Nature Genet 18, 338–343
    OpenUrlCrossRefPubMedWeb of Science
    1. Kretschmar M.,
    2. Liu F.,
    3. Hata A.,
    4. Doody J.,
    5. Massague J.
    (1997) The TGF-mediator Smad1 is directly phosphorylated and functionally activated by the BMP receptor kinase. Genes Dev 11, 984–995
    OpenUrlAbstract/FREE Full Text
    1. Liu F.,
    2. Ventura F.,
    3. Doody J.,
    4. Massague J.
    (1995) Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs. Mol. Cell. Biol 15, 3479–3486
    OpenUrlAbstract/FREE Full Text
    1. Macias-Silva M.,
    2. Hoodless P. A.,
    3. Tang S. J.,
    4. Buchwald M.,
    5. Wrana J. L.
    (1998) Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J. Biol. Chem 273, 25628–25636
    OpenUrlAbstract/FREE Full Text
    1. Maeno M.,
    2. Ong R. C.,
    3. Suzuki A.,
    4. Ueno N.,
    5. Kung H.
    (1994) A truncated bone morphogenetic protein receptor alters the fate of ventral mesoderm to dorsal mesoderm: roles of animal pole tissue in the development of the ventral mesoderm. Proc. Natl. Acad. Sci. USA 91, 10260–10264
    OpenUrlAbstract/FREE Full Text
    1. Massague J.
    (1998) TGF-signal transduction. Annu. Rev. Biochem 67, 753–791
    OpenUrlCrossRefPubMedWeb of Science
    1. Mintzer K.,
    2. Lee M. A.,
    3. Runke G.,
    4. Trout J.,
    5. Whitman M.,
    6. Mullins M. C.
    (2001) lost-a-fin encodes a type I BMP receptor, Alk8, acting maternally and zygotically in dorsoventral pattern formation. Development 128, 859–869
    OpenUrlAbstract
    1. Mullins M. C.,
    2. Hammerschmidt M.,
    3. Kane D. A.,
    4. Odenthal J.,
    5. Brand M.,
    6. van Eeden F. J. M.,
    7. Furutani-Seiki M.,
    8. Granato M.,
    9. Haffter P.,
    10. Heisenberg C.-P.,
    11. et al.
    (1996) Genes establishing dorsoventral pattern formation in the zebrafish embryo: the ventral specifying genes. Development 123, 81–93
    OpenUrlAbstract/FREE Full Text
    1. Nasevicius A.,
    2. Ekker. S.C.
    (2000) Effective targeted gene knockdown in zebrafish. Nat. Genet 26, 216–220
    OpenUrlCrossRefPubMedWeb of Science
    1. Nellen D.,
    2. Affolter M.,
    3. Basler K.
    (1994) Receptor serine/threonine kinases implicated in the control of Drosophila body pattern by decapentaplegic. Cell 78, 225–237
    OpenUrlCrossRefPubMedWeb of Science
    1. Neul J. L.,
    2. Ferguson E. L.
    (1998) Spatially restricted activation of the SAX receptor by SCW modulates DPP/TKV signaling in Drosophila dorsal-ventral patterning. Cell 95, 483–494
    OpenUrlCrossRefPubMedWeb of Science
    1. Nguyen M.,
    2. Park S.,
    3. Marques G.,
    4. Arora K.
    (1998) Interpretation of a BMP activity gradient in Drosophila embryos depends on synergistic singnaling by two type I receptors, SAX and TKV. Cell 95, 495–506
    OpenUrlCrossRefPubMedWeb of Science
    1. Nguyen V. H.,
    2. Schmid B.,
    3. Trout J.,
    4. Connors S.A.,
    5. Ekker M.,
    6. Mullins M. C.
    (1998) Ventral and lateral regions of the zebrafish gastrula, including the neural crest progenitors, are established by a bmp2b/swirl pathway of genes. Dev. Biol 199, 93–110
    OpenUrlCrossRefPubMedWeb of Science
    1. Nikaido M.,
    2. Tada M.,
    3. Saij T.,
    4. Ueno N.
    (1997) Conservation of BMP signaling in zebrafish mesoderm patterning. Mech. Dev 61, 75–88
    OpenUrlCrossRefPubMedWeb of Science
    1. Nikaido M.,
    2. Tada M.,
    3. Takeda H.,
    4. Kuroiwa A.,
    5. Ueno N.
    (1999) In vivo analysis using variants of zebrafish BMPR-1A: range of action and involvement of BMP in ectoderm patterning. Development 126, 181–190
    OpenUrlAbstract
    1. Nikaido M.,
    2. Tada M.,
    3. Ueno N.
    (1999) Restricted expression of the receptor serine/threonine kinase BMPR-IB in zebrafish. Mech. Dev 82, 219–222
    OpenUrlCrossRefPubMedWeb of Science
    1. Nordness S.,
    2. Krauss S.,
    3. Johansen T.
    (1994) cDNA sequence of zebrafish (Brachydanio rerio) translation elongation factor-1 alpha: molecular phylogeny of eukaryotes based on elongation factor-1 alpha protein sequences. Biochim. Biophys. Acta 1219, 529–532
    OpenUrlPubMed
    1. Oxtoby E.,
    2. Jowett T.
    (1993) Cloning of the zebrafish krox-20 (krx-20) and its expression during hindbrain development. Nucleic Acids Res 21, 1087–1095
    OpenUrlAbstract/FREE Full Text
    1. Piccolo S. Y.,
    2. Sasai Y.,
    3. Lu B.,
    4. De Robertis E. M.
    (1996) A possible molecular mechanism for Spemann organizer function: inhibition of ventral signals by direct binding of Chordin to BMP-4. Cell 85, 589–598
    OpenUrl
    1. Piccolo S.,
    2. Agius E.,
    3. Lu B.,
    4. Goodman S.,
    5. Dale L.,
    6. DeRobertis E. M.
    (1997) Cleavage of Chordin by Xolloid metalloprotease suggests a role for proteolytic processing in the regulation of Spemann organizer activity. Cell 91, 407–416
    OpenUrlCrossRefPubMedWeb of Science
    1. Rupp R. A. W.,
    2. Snider L.,
    3. Weintraub H.
    (1994) Xenopus embryos regulate the nuclear localization of XMyoD. Genes Dev 8, 1311–1323
    OpenUrlAbstract/FREE Full Text
    1. Schmid B.,
    2. Furthauer M.,
    3. Conners S. A.,
    4. Trout J.,
    5. Thisse B.,
    6. Thisse C.,
    7. Mullins M. C.
    (2000) Equivalent genetic roles of bmp7 / snailhouse and bmp2b / swirl in dorsoventral pattern formation. Development 127, 957–967
    OpenUrlAbstract
    1. Schmidt J. E.,
    2. Suzuki A.,
    3. Ueno N.,
    4. Kimelman D.
    (1995) Localized BMP-4 mediates dorsal/ventral patterning in the early Xenopus embryo. Dev. Biol 169, 37–50
    OpenUrlCrossRefPubMedWeb of Science
    1. Schulte-Merker S.,
    2. Lee L. J.,
    3. McMahon A. P.,
    4. Hammerschmidt M.
    (1997) The zebrafish organizer requires chordino. Nature 387, 862–863
    OpenUrlCrossRefPubMed
    1. Solnica-Krezel L.,
    2. Stemple D. L.,
    3. Mountcastle-Shah E.,
    4. Rangini Z.,
    5. Neuhauss S. C. F.,
    6. Malicki J.,
    7. Schier A.,
    8. Stanier D. Y. R.,
    9. Zwartkruis F.,
    10. Abdelilah S.,
    11. Driever W.
    (1996) Mutations affecting cell fates and cellular rearrangements during gastrulation in the zebrafish. Development 123, 67–80
    OpenUrlAbstract/FREE Full Text
    1. Suzuki A.,
    2. Thies R. S.,
    3. Yamayi N.,
    4. Song J. J.,
    5. Wozney J. M.,
    6. Murakami K.,
    7. Ueno N.
    (1994) A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad. Sci. USA 91, 10255–10259
    OpenUrlAbstract/FREE Full Text
    1. ten Dijke P.,
    2. Yamashita H.,
    3. Sampath T. K.,
    4. Reddi H.,
    5. Estevez M.,
    6. Riddle D. L.,
    7. Ichijo H.,
    8. Heldin C.-H.,
    9. Miyazono K.
    (1994) Identification of type I receptors for Osteogenic Protein-1 and Bone Morphogenetic Protein-4. J. Biol. Chem 269, 16985–16988
    OpenUrlAbstract/FREE Full Text
    1. Wieser R.,
    2. Wrana J.,
    3. Massague J.
    (1995) GS domain mutations that constitutively activate TR-1, a downstream signaling component in the TGF receptor complex. EMBO J 14, 2199–2208
    OpenUrlPubMedWeb of Science
    1. Wilson P. A.,
    2. Hemmati-Brivanlou A.
    (1995) Induction of epidermis and inhibition of neural fate by Bmp-4. Nature 376, 331–333
    OpenUrlCrossRefPubMedWeb of Science
    1. Wrana J. L.,
    2. Tran H.,
    3. Attisano L.,
    4. Arora K.,
    5. Childs S. R.,
    6. Massague J.,
    7. O'Connor M. B.
    (1994) Two distinct transmembrane serine/threonine kinases from Drosophila melanogaster form an activin receptor complex. Mol. Cell. Biol 14, 944–950
    OpenUrlAbstract/FREE Full Text
    1. Yamashita H.,
    2. ten Dijke P.,
    3. Huylebroeck D.,
    4. Sampath T. K.,
    5. Andries M.,
    6. Smith J. C.,
    7. Heldin C. H.,
    8. Miyazono K.
    (1995) Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects. J. Cell. Biol 130, 217–226
    OpenUrlAbstract/FREE Full Text
    1. Yelick P. C.,
    2. Abduljabbar T.S.,
    3. Stashenko P.
    (1998) zALK-8, a novel type I serine/threonine kinase receptor, is expressed throughout early zebrafish development. Dev. Dyn 211, 352–361
    OpenUrlCrossRefPubMed
Back to top

 Download PDF

Email
JOURNAL ARTICLES
The type I serine/threonine kinase receptor Alk8/Lost-a-fin is required for Bmp2b/7 signal transduction during dorsoventral patterning of the zebrafish embryo
H. Bauer, Z. Lele, G.J. Rauch, R. Geisler, M. Hammerschmidt
Development 2001 128: 849-858;
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

The Node is looking for a new Community Manager!

If you're interested in science communication, publishing and the developmental biology community, we're hiring for a new Community Manager for our community site, the Node.

The position is an exciting opportunity to develop an already successful and well-known site, engaging with the academic, publishing and online communities. Find out more and how to apply.

Upcoming special issue: call for papers

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

The special issue welcomes Review articles as well as Research articles, and will be widely promoted online and at key global conferences.

The people behind the papers - Clément Dubois, Shivam Gupta, Andrew Mugler and Marie-Anne Félix

A new paper investigates the robustness of neuroblast migration in the C. elegans larva in the face of both genetic and environmental variation. In an interview, the paper's four authors tell us more about the story.

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. Every talk is recorded and since launching in August last year, the series has clocked up almost 10k views on YouTube.

Here, Swann Floc'hlay discusses her work modelling dorsal-ventral axis specification in the sea urchin embryo.

Save your spot at our next session:

14 April
Time: 17:00 BST
Chaired by: François Guillemot

12 May
Time: TBC
Chaired by: Paola Arlotta

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