Advertisement
JOURNAL ARTICLES
Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb
P.H. Francis, M.K. Richardson, P.M. Brickell, C. Tickle
Development 1994 120: 209-218;

Summary

We show here that bone morphogenetic protein 2 (BMP-2) is involved in patterning the developing chick limb. During early stages of limb development, mesenchymal expression of the Bmp-2 gene is restricted to the posterior part of the bud, in a domain that colocalizes with the polarizing region. The polarizing region is a group of cells at the posterior margin of the limb bud that can respecify the anteroposterior axis of the limb when grafted anteriorly and can activate expression of genes of the HoxD complex. We dissect possible roles of BMP-2 in the polarizing region signalling pathway by manipulating the developing wing bud. Retinoic acid application, which mimics the effects of polarizing region grafts, activates Bmp-2 gene expression in anterior cells. This shows that changes in anteroposterior pattern are correlated with changes in Bmp-2 expression. When polarizing region grafts are placed at the anterior margin of the wing bud, the grafts continue to express the Bmp-2 gene and also activate Bmp-2 expression in the adjacent anterior host mesenchyme. These data suggest that BMP-2 is part of the response pathway to the polarizing signal, rather than being the signal itself. In support of this, BMP-2 protein does not appear to have any detectable polarizing activity when applied to the wing bud. The pattern of Bmp-4 gene expression in the developing wing bud raises the possibility that BMP-2 and BMP-4 could act in concert. There is a close relationship, both temporal and spatial, between the activation of the Bmp-2 and Hoxd-13 genes in response to retinoic acid and polarizing region grafts, suggesting that expression of the two genes might be linked.

REFERENCES

    1. Chomczynski P.,
    2. Sacchi N.
    (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt. Biochem 162, 156–159
    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. Davidson D.,
    2. Graham E.,
    3. Sime C.,
    4. Hill R.
    (1988) A gene with sequence similarity to Drosophila engrailed is expressed during the development of the neural tube and vertebrate in the mouse. Development 104, 305–316
    OpenUrlAbstract
    1. Devlin C. J.,
    2. Brickell P. M.,
    3. Taylor E. R.,
    4. Hornbruch A.,
    5. Craig R. K.,
    6. Wolpert L.
    (1988) In situ hybridisation reveals different spatial localisation of mRNAs for type I and type II collagen in the chick limb bud. Development 103, 111–118
    OpenUrlAbstract
    1. Dickinson M. E.,
    2. Kobrin M. S.,
    3. Silan C. M.,
    4. Kingsley D. M.,
    5. Justice M. J.,
    6. Miller D. A.,
    7. Ceci J. D.,
    8. Lock L. F.,
    9. Lee A.,
    10. Buchberg A. M.,
    11. Siracusa L. D.,
    12. Lyons K. M.,
    13. Derynck R.,
    14. Hogan B. L. M.,
    15. Copeland N. G.,
    16. Jenkins N. A.
    (1990) Chromosomal localization of seven members of the murine TGF-superfamily suggests close linkage to several morphogenetic mutant loci. Genomics 6, 505–520
    OpenUrlCrossRefPubMedWeb of Science
    1. Feinberg A. P.,
    2. Vogelstein B.
    (1984) A technique for radiolabelling DNA restriction endonuclease fragments to a high specific activity. Analyt. Biochem 137, 266–267
    OpenUrlCrossRefPubMedWeb of Science
    1. Ferguson E. L.,
    2. Anderson K. V.
    (1992) decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell 71, 451–461
    OpenUrlCrossRefPubMedWeb of Science
    1. Hamburger V.,
    2. Hamilton H. L.
    (1951) A series of normal stages in the development of the chick embryo. J. Morph 88, 49–92
    OpenUrlCrossRefPubMedWeb of Science
    1. Hoffman F. M.
    (1991) Transforming growth factor--related genes in Drosophila and vertebrate development. Current Opinion Cell Biol 3, 947–952
    OpenUrlCrossRefPubMed
    1. Honig L. S.,
    2. Summerbell D.
    (1985) Maps of strength of positional signalling activity in the developing chick wing bud. J. Embryol. Exp. Morph 87, 163–174
    OpenUrlPubMedWeb of Science
    1. Hornbruch A.,
    2. Wolpert L.
    (1991) The spatial and temporal distribution of polarizing activity in the flank of the pre-limb-bud stages in the chick embryo. Development 111, 725–731
    OpenUrlAbstract
    1. Hsueh A. J. W.,
    2. Dahl K. D.,
    3. Vaughan J.,
    4. Tucker E.,
    5. Rivier J.,
    6. Bardin C. W.,
    7. Vale W.
    (1987) Heterodimers and homodimers of inhibin subunits have different paracrine action in the modulation of luteinizing hormone-stimulated androgen biosynthesis. Proc. natn. Acad. Sci. USA 84, 5082–5086
    OpenUrlAbstract/FREE Full Text
    1. Izpisúa-Belmonte J.-C.,
    2. Tickle C.,
    3. Dolle P.,
    4. Wolpert L.,
    5. Duboule D.
    (1991) Expression of the homeobox Hox-4 genes and the specification of position in chick wing development. Nature 350, 585–589
    OpenUrlCrossRefPubMed
    1. Izpisúa-Belmonte. J.-C.,
    2. Brown J. M.,
    3. Crawley A.,
    4. Duboule D.,
    5. Tickle C.
    (1992) Hox-4 gene expression in mouse/chicken heterospecific grafts of signalling regions to limb buds reveals similarities in patterning mechanisms. Development 115, 553–560
    OpenUrlAbstract
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Hogan B. L. M.
    (1991) Involvement of Bone Morphogenetic Protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111, 531–542
    OpenUrlAbstract
    1. Jones C. M.,
    2. Lyons K. M.,
    3. Lapan P. M.,
    4. Wright C. 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. Lyons K. M.,
    2. Pelton R. W.,
    3. Hogan B. L. M.
    (1989) Patterns of expression of murine Vgr-1 and BMP-2a RNA suggest that transforming growth factor--like genes coordinately regulate aspects of embryonic development. Genes Dev 3, 1657–1668
    OpenUrlAbstract/FREE Full Text
    1. Maccabe A. B.,
    2. Gasseling M. T.,
    3. Saunders J. W.
    (1973) Spatiotemporal distribution of mechanisms that control outgrowth and anteroposterior polarization of the limb bud in the chick embryo. Mech. Ageing Develop 2, 1–12
    OpenUrlCrossRefPubMed
    1. Niswander L.,
    2. Martin G. R.
    (1992) Fgf-4 expression during gastrulation, myogenesis, limb and tooth development in the mouse. Development 114, 755–768
    OpenUrlAbstract
    1. Niswander L.,
    2. Martin G. R.
    (1993) FGF 4 and BMP-2 have opposite effects on limb growth. Nature 361, 68–71
    OpenUrlCrossRefPubMed
    1. Nohno T.,
    2. Noji S.,
    3. Koyama E.,
    4. Ohyama K.,
    5. Myokai F.,
    6. Kuroiwa A.,
    7. Saito T.,
    8. Taniguchi S.
    (1991) Involvement of the Chox-4 chicken homeobox genes in determination of anteroposterior axial polarity during limb development. Cell 64, 1197–1205
    OpenUrlCrossRefPubMedWeb of Science
    1. Oliver G.,
    2. De Robertis E. M.,
    3. Wolpert L.,
    4. Tickle C.
    (1990) Expression of a homeobox gene in the chick wing bud following application of retinoic acid and grafts of polarizing region tissue. EMBO J 9, 3093–3101
    OpenUrlPubMedWeb of Science
    1. Panganiban G. E. F.,
    2. Reuter R.,
    3. Scott M. P.,
    4. Hoffman F. M.
    (1990) A Drosophila growth factor homologue, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis. Development 110, 1041–1050
    OpenUrlAbstract/FREE Full Text
    1. Rosen V.,
    2. Thies R. S.
    (1992) The BMP proteins in bone formation and repair. Trends Genet 8, 97–102
    OpenUrlCrossRefPubMedWeb of Science
    1. Rowe A.,
    2. Richman J. M.,
    3. Brickell P. M.
    (1991) Retinoic acid treatment alters the distribution of retinoic acid receptor-transcripts in the embryonic chick face. Development 111, 1007–1016
    OpenUrlAbstract/FREE Full Text
    1. Sampath T. K.,
    2. Coughlin J. E.,
    3. Whetstone R. M.,
    4. Banach D.,
    5. Corbett C.,
    6. Ridge R. J.,
    7. Özkaynak E.,
    8. Oppermann H.,
    9. Rueger D. C.
    (1990) Bovine osteogenic protein is composed of OP-1 and BMP-2A, two members of the transforming growth factor-superfamily. J. Biol. Chem 265, 13198–13205
    OpenUrlAbstract/FREE Full Text
    1. Smith J. C.
    (1979) Evidence for a positional memory in the development of the chick wing bud. J. Embryol. Exp. Morph 52, 105–113
    OpenUrlPubMed
    1. Smith J. C.,
    2. Cooke J.,
    3. Green J. B. A.,
    4. Howes G.,
    5. Symes K.
    (1989) Inducing factors and the control of mesodermal pattern in Xenopus laevis. Development 107, 149–160
    1. Szabo G.
    (1955) A modification of the technique of ‘skin splitting’ with trypsin. J. Path. Bact 70, 545–.
    1. Tabin C.J.
    (1991) Retinoids, homeoboxes, and growth factors: toward molecular models for limb development. Cell 66, 199–217
    OpenUrlCrossRefPubMedWeb of Science
    1. Thomsen G.H.,
    2. Melton D.A.
    (1993) Processed Vg1 protein is an axial mesoderm inducer in Xenopus. Cell 74, 433–441
    OpenUrlCrossRefPubMedWeb of Science
    1. Tickle C. A.,
    2. Summerbell D.,
    3. Wolpert L.
    (1975) Positional signalling and specification of digits in chick limb morphogenesis. Nature 254, 199–202
    OpenUrlCrossRefPubMedWeb of Science
    1. Tickle C.,
    2. Shellswell G.,
    3. Crawley A.,
    4. Wolpert L.
    (1976) Positional signalling by mouse limb polarising region in the chick wing bud. Nature 259, 396–397
    OpenUrlCrossRefPubMed
    1. Tickle C.,
    2. Alberts B.,
    3. Lee J.,
    4. Wolpert L.
    (1982) Local application of retinoic acid to the limb bud mimics the action of the polarising region. Nature 296, 564–565
    OpenUrlCrossRefPubMed
    1. Tickle C.,
    2. Lee J.,
    3. Eichele G.
    (1985) A quantitative analysis of the effect of all-trans-retinoic acid on the pattern of chick wing development. Dev. Biol 197, 27–36
    OpenUrl
    1. Tickle C.,
    2. Crawley A.,
    3. Farrar J.
    (1989) Retinoic acid application to chick wing buds leads to a dose-dependent reorganization of the apical ectodermal ridge that is mediated by the mesenchyme. Development 106, 691–705
    OpenUrlAbstract/FREE Full Text
    1. Wanek N.,
    2. Gardiner D. M.,
    3. Muneoka K.,
    4. Bryant S. V.
    (1991) Conversion by retinoic acid of anterior cells into ZPA cells in the chick wing bud. Nature 350, 81–83
    OpenUrlCrossRefPubMed
    1. Wozney J. M.
    (1989) Bone morphogenetic proteins. Prog. Growth Factor Res 1, 267–280
    OpenUrlCrossRefPubMed
    1. Wozney J. M.,
    2. Rosen V.,
    3. Celeste A. J.,
    4. Mitsock L. M.,
    5. Whitters M. J.,
    6. Kriz R. W.,
    7. Hewick R. M.,
    8. Wang E. A.
    (1988) Novel regulators of bone formation: molecular clones and activities. Science 242, 1528–1534
    OpenUrlAbstract/FREE Full Text
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Bone morphogenetic proteins and a signalling pathway that controls patterning in the developing chick limb
P.H. Francis, M.K. Richardson, P.M. Brickell, C. Tickle
Development 1994 120: 209-218;
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

A new society for regenerative biologists

Kenneth Poss and Elly Tanaka announce the launch of the International Society for Regenerative Biology (ISRB), which will promote research and education in the field of regenerative biology.

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.

An interview with Cagney Coomer

Over a virtual chat, we spoke to Cagney Coomer about her experiences in the lab, the classroom and the community centre, and why she thinks outreach and role models are vital to science.

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.