Advertisement
JOURNAL ARTICLES
Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1
P.A. Wilson, G. Lagna, A. Suzuki, A. Hemmati-Brivanlou
Development 1997 124: 3177-3184;

Summary

Morphogens are thought to establish pattern in early embryos by specifying several cell fates along a gradient of concentration; a well-studied example is the Drosophila protein decapentaplegic (DPP) acting in the wing disc. Recent work has established that bone morphogenetic protein 4 (BMP4), the vertebrate homologue of DPP, controls the fundamental choice between neural and epidermal fates in the vertebrate ectoderm, under the control of antagonists secreted by the organizer region of the mesoderm. We now show that BMP4 can act as a morphogen, evoking distinct responses in Xenopus ectodermal cells at high and low concentrations, in a pattern consistent with the positions of the corresponding cell types in the embryo. Moreover, this complex cellular response to extracellular BMP4 concentration does not require subsequent cell-cell communication and is thus direct, as required of a classical morphogen. We also show that the same series of cell types--epidermis, cement gland and neural tissue--can be produced by progressively inhibiting endogenous BMP signaling with specific antagonists, including the organizer factor noggin. Finally, expression of increasing doses of the signal transduction molecule Smad1 accurately reproduces the response to BMP4 protein. Since Smads have been shown to act in the nucleus, this finding implies a direct translation of extracellular morphogen concentration into transcription factor activity. We propose that a graded distribution of BMP activity controls the specification of several cell types in the gastrula ectoderm and that this extracellular gradient acts by establishing an intracellular and then nuclear gradient of Smad activity.

REFERENCES

    1. Bolce M. E.,
    2. Hemmati-Brivanlou A.,
    3. Kushner P. D.,
    4. Harland R. M.
    (1992) Ventral ectoderm of Xenopus forms neural tissue, including hindbrain, in response to activin. Development 115, 681–688
    OpenUrlAbstract
    1. Bradley L.,
    2. Wainstock D.,
    3. Sive H.
    (1996) Positive and negative signals modulate formation of the Xenopus cement gland. Development 122, 2739–2750
    OpenUrlAbstract
    1. Chen X.,
    2. Rubock M. J.,
    3. Whitman M.
    (1996) A transcriptional partner for MAD proteins in TGF-beta signalling. Nature 383, 691–696
    OpenUrlCrossRefPubMedWeb of Science
    1. Dickinson M. E.,
    2. Selleck M. A. J.,
    3. McMahon A. P.,
    4. Bronner-Fraser M.
    (1995) Dorsalization of the neural tube by the non-neural ectoderm. Development 121, 2099–2106
    OpenUrlAbstract
    1. Doniach T.
    (1995) Basic FGF as an inducer of anteroposterior neural pattern. Cell 83, 1067–70
    OpenUrlCrossRefPubMedWeb of Science
    1. Drysdale T.,
    2. Elinson R. P.
    (1993) Inductive events in the patterning of the Xenopus laevis hatching and cement glands, two cell types which delimit head boundaries. Dev. Biol 158, 245–253
    OpenUrlCrossRefPubMed
    1. Essex L. J.,
    2. Mayor R. M.,
    3. Sargent M. G.
    (1993) Expression of Xenopus snail in mesoderm and prospective neural fold ectoderm. Devel. Dynamics 198, 108–122
    OpenUrlPubMedWeb of Science
    1. Ferguson E.,
    2. Anderson K.
    (1992) Decapentaplegic acts as a morphogen to organize dorsal-ventral pattern in the Drosophila embryo. Cell 71, 451–461
    OpenUrlCrossRefPubMedWeb of Science
    1. Graff J.,
    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. Graff J. M.,
    2. Bansal A.,
    3. Melton D. A.
    (1996) Xenopus Mad proteins transduce distinct subsets of signals for the TGFβ superfamily. Cell 85, 479–487
    OpenUrlCrossRefPubMedWeb of Science
    1. Grant P.,
    2. Wacaster J. F.
    (1972) The amphibian grey crescent—a site of developmental information?. Dev. Biol 28, 454–471
    OpenUrlCrossRefPubMedWeb of Science
    1. Green J. B. A.,
    2. New H. V.,
    3. Smith J. C.
    (1992) Responses of embryonic Xenopus cells to activin and FGF are separated by multiple dose thresholds and correspond to distinct axes of the mesoderm. Cell 71, 731–739
    OpenUrlCrossRefPubMedWeb of Science
    1. Green J. B. A.,
    2. Howes G.,
    3. Symes K.,
    4. Cooke J.,
    5. Smith J. C.
    (1990) The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF. Development 108, 173–183
    OpenUrlAbstract
    1. Green J. B. A.,
    2. Smith J. C.
    (1990) Graded changes in dose of a Xenopus activin A homologue elicit stepwise transitions in embryonic cell fate. Nature 347, 391–394
    OpenUrlCrossRefPubMed
    1. Gurdon J. B.,
    2. Harger P.,
    3. Mitchell A.,
    4. Lemaire P.
    (1994) Activin signalling and response to a morphogen gradient. Nature 371, 487–492
    OpenUrlCrossRefPubMed
    1. Gurdon J. B.,
    2. Mitchell A.,
    3. Mahony D.
    (1995) Direct and continuous assessment by cells of their position in a morphogen gradient. Nature 376, 520–1
    OpenUrlCrossRefPubMed
    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. Hoodless P. A.,
    2. Haerry T.,
    3. Abdollah S.,
    4. Stapleton M.,
    5. O'Connor M. B.,
    6. Attisano L.,
    7. Wrana J. L.
    (1996) MADR1, a MAD-related protein that functions in BMP2 signalling pathways. Cell 85, 489–500
    OpenUrlCrossRefPubMedWeb of Science
    1. Jonas E.,
    2. Sargent T. D.,
    3. Dawid I. B.
    (1985) Epidermal keratin gene expressed in embryos of Xenopus laevis. Proc. Natl. Acad. Sci. USA 82, 5413–5417
    OpenUrlAbstract/FREE Full Text
    1. Kao K.,
    2. Elinson R.
    (1988) The entire mesodermal mantle behaves as a Spemann organizer in dorsoanterior enhanced Xenopus embryos. Dev. Biol 127, 64–77
    OpenUrlCrossRefPubMedWeb of Science
    1. Kintner C. R.,
    2. Melton D. A.
    (1987) Expression of Xenopus N-CAM RNA in ectoderm is an early response to neural induction. Development 99, 311–325
    OpenUrlAbstract
    1. Krieg P.,
    2. Varnum S.,
    3. Wormington M.,
    4. Melton D. A.
    (1989) The mRNA encoding elongation factor 1(EF1) is a major transcript at the mid blastula transition in Xenopus. Dev. Biol 133, 93–100
    OpenUrlCrossRefPubMedWeb of Science
    1. Lawrence P. A.
    (1966) Gradients in the insect segment: the orientation of hairs in the milkweed bug Oncopeltus fasciatus. J. Exp. Biol 44, 607–620
    OpenUrlAbstract/FREE Full Text
    1. Lecuit T.,
    2. Brook W. J.,
    3. Ng M.,
    4. Calleja M.,
    5. Sun H.,
    6. Cohen S. M.
    (1996) Two distinct mechanisms for long-range patterning by Decapentaplegic in the Drosophila wing. Nature 381, 387–393
    OpenUrlCrossRefPubMed
    1. Liem K. F.,
    2. Tremml G.,
    3. Roelink H.,
    4. Jessell T. M.
    (1995) Dorsal differentiation of neural plate cells induced by BMP-mediated signals form epidermal ectoderm. Cell 82, 969–79
    OpenUrlCrossRefPubMedWeb of Science
    1. Liu F.,
    2. Hata A.,
    3. Baker J.,
    4. Doody J.,
    5. Cárcamo J.,
    6. Harland R.,
    7. Massague J.
    (1996) A human Mad protein acting as a BMP-regulated transcriptional activator. Nature 381, 62–623
    1. London C.,
    2. Akers T.,
    3. Phillips C. R.
    (1988) Expression of Epi1, an epidermal specific marker, in Xenopus laevis embryos is specified prior to gastrulation. Dev. Biol 129, 380–389
    OpenUrlCrossRefPubMedWeb of Science
    1. Mancilla A.,
    2. Mayor R.
    (1996) Neural crest formation in Xenopus laevis: mechanisms of Xslug induction. Dev. Biol 177, 580–589
    OpenUrlCrossRefPubMedWeb of Science
    1. Mayor R.,
    2. Morgan R.,
    3. Sargent M. G.
    (1995) Induction of the prospective neural crest of Xenopus. Development 121, 767–777
    OpenUrlAbstract
    1. Moury J. M.,
    2. Jacobson A. G.
    (1990) The origins of neural crest cells in the Axolotl. Dev. Biol 141, 243–253
    OpenUrlCrossRefPubMedWeb of Science
    1. Nellen D.,
    2. Burke R.,
    3. Struhl G.,
    4. Basler K.
    (1996) Direct and long-range action of a DPP morphogen gradient. Cell 85, 357–368
    OpenUrlCrossRefPubMedWeb of Science
    1. Piccolo S.,
    2. Sasai Y.,
    3. Lu B.,
    4. De Robertis E. M.
    (1996) Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP4. Cell 86, 589–598
    OpenUrlCrossRefPubMedWeb of Science
    1. Reilly K. M.,
    2. Melton D. A.
    (1996) Short-range signaling by candidate morphogens of the TGF-beta family and evidence for a relay mechanism of induction. Cell 86, 743–754
    OpenUrlCrossRefPubMedWeb of Science
    1. Sargent T. D.,
    2. Jamrich M.,
    3. Dawid I. B.
    (1986) Cell interactions and the control of gene activity during early development of Xenopus laevis. Dev. Biol 114, 238–246
    OpenUrlCrossRefPubMedWeb of Science
    1. Sasai Y.,
    2. Lu B.,
    3. Steinbeisser H.,
    4. De Robertis E. M.
    (1995) Regulation of neural induction by the Chd and Bmp-4 antagonistic patterning signals in Xenopus. Nature 376, 333–336
    OpenUrlCrossRefPubMed
    1. Sharpe C. R.,
    2. Fritz A.,
    3. De Robertis E. M.,
    4. Gurdon J. B.
    (1987) A homeobox-containing marker of posterior neural differentiation shows the importance of predetermination in neural induction. Cell 50, 749–758
    OpenUrlCrossRefPubMedWeb of Science
    1. Sive H.,
    2. Bradley L.
    (1996) A sticky problem—the Xenopus cement gland as a paradigm for anteroposterior patterning. Devel. Dynamics 205, 265–280
    OpenUrlCrossRefPubMedWeb of Science
    1. Smith J. C.,
    2. Price B. M.,
    3. Green J. B.,
    4. Weigel D.,
    5. Herrmann B. G.
    (1991) Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction. Cell 67, 79–87
    OpenUrlCrossRefPubMedWeb of Science
    1. Smith W. B.,
    2. Harland R. M.
    (1992) Expression Cloning of noggin, a New Dorsalizing Factor Localized to the Spemann Organizer in Xenopus Embryos. Cell 70, 829–840
    OpenUrlCrossRefPubMedWeb of Science
    1. Sokol S.,
    2. Melton D. A.
    (1991) Pre-existent pattern in Xenopus animal pole cells revealed by induction with activin. Nature 351, 409–411
    OpenUrlCrossRefPubMedWeb of Science
    1. Suzuki A.,
    2. Chang C.,
    3. Yingling M.,
    4. Wang X.-F.,
    5. Hemmati-Brivanlou A.
    (1997) Smad5 induces ventral fates in Xenopus embryo. Dev. Biol 184, 402–405
    OpenUrlCrossRefPubMedWeb of Science
    1. Suzuki A.,
    2. Shioda N.,
    3. Ueno N.
    (1995) Bone morphogenetic protein acts as a ventral mesoderm modifier in early Xenopus embryos. Develop. Growth Differ 37, 581–588
    OpenUrlCrossRef
    1. Suzuki A.,
    2. Theis R. S.,
    3. Yamaji N.,
    4. Song J. J.,
    5. Wozney J.,
    6. Murakami K.,
    7. Ueno N.
    (1994) A truncated BMP receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc. Natl. Acad. Sci. USA 91, 10255–1259
    OpenUrlAbstract/FREE Full Text
    1. Thomsen G.
    (1996) Xenopus mothers against decapentaplegic is an embryonic ventralizing agent that acts downstream of the BMP-2/4 receptor. Development 122, 2359–2366
    OpenUrlAbstract
    1. Turing A.
    (1952) The chemical basis of morphogenesis. Philos. Trans. R. Soc. Lond 237, 37–72
    OpenUrlCrossRef
    1. Weinstein D. C.,
    2. Hemmati-Brivanlou A.
    (1997) Neural induction in Xenopus laevis; evidence for the default model. Current Opinion in Neurobiology 7, 7–12
    OpenUrlCrossRefPubMed
    1. Wharton K. A.,
    2. Ray R. P.,
    3. Gelbart W. M.
    (1993) An activity gradient of decapentaplegic is necessary for the specification of dorsal pattern elements in the Drosophila embryo. Development 117, 807–822
    OpenUrlAbstract
    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. Wilson P. A.,
    2. Melton D. A.
    (1994) Mesodermal patterning by an inducer gradient depends on secondary cell-cell communication. Current Biology 4, 676–686
    OpenUrlCrossRefPubMedWeb of Science
    1. Wolpert L.
    (1969) Positional information and the spatial pattern of cellular differentiation. J. Theor. Biol 25, 1–47
    OpenUrlCrossRefPubMedWeb of Science
    1. Xu R. H.,
    2. Kim J.,
    3. Taira M.,
    4. Zhan S.,
    5. Sredni D.,
    6. Kung H. F.
    (1995) A dominant-negative bone morphogenetic protein 4 receptor causes neuralization in Xenopus ectoderm. Biochem. Biophys. Res. Commun 212, 212–219
    OpenUrlCrossRefPubMedWeb of Science
    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. Zimmerman L. B.,
    2. De Jesus-Escobar J. M.,
    3. Harland R. M.
    (1996) The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell 86, 599–606
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
JOURNAL ARTICLES
Concentration-dependent patterning of the Xenopus ectoderm by BMP4 and its signal transducer Smad1
P.A. Wilson, G. Lagna, A. Suzuki, A. Hemmati-Brivanlou
Development 1997 124: 3177-3184;
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.