The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling
Open accessAbstract
Despite extensive studies on the anterior-posterior (AP) axis formation of limb buds, mechanisms that specify digit identities along the AP axis remain obscure. Using the four-digit chick leg as a model, we report here that Tbx2 and Tbx3 specify the digit identities of digits IV and III, respectively. Misexpression of Tbx2 and Tbx3 induced posterior homeotic transformation of digit III to digit IV and digit II to digit III, respectively. Conversely, misexpression of their mutants VP16 Delta Tbx2 and VP16 Delta Tbx3 induced anterior transformation. In both cases, alterations in the expression of several markers (e.g., BMP2, Shh, and HoxD genes) were observed. In addition, Tbx2 and Tbx3 rescued Noggin-mediated inhibition of interdigital BMP signaling, signaling which is pivotal in establishing digit identities. Hence, we conclude that Tbx3 specifies digit III, and the combination of Tbx2 and Tbx3 specifies digit IV, acting together with the interdigital BMP signaling cascade.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Thus, critical morphogenic and oncogenic signaling pathways, such as BMPs17, Shh18, TGF-β19, FGFs20, Wnt/β-catenin21, as well as BRAF/MAPK pathway, participate in TBX3 expression regulation, mostly at the transcriptional level12,15.”
From Proteostatic reactivation of the developmental transcription factor TBX3 drives BRAF/MAPK-mediated tumorigenesis (2024) · cites this paper as [18]
Citations
Cites
Boussif, O., Lezoualc’h, F., Zanta, M. A., Djavaheri‐Mergny, M., Scherman, D., DEMENEIX, B. A., & Behr, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.16.7297 · Cited by 6,256
Sonic hedgehog mediates the polarizing activity of the ZPA
Riddle, R. D., Johnson, R. L., Laufer, E., & Tabin, C. J. (1993) · Cell · doi:10.1016/0092-8674(93)90626-2 · Cited by 2,285
Langdale, J. A. (1994) · Springer eBooks · doi:10.1007/978-1-4612-2694-9_18 · Cited by 869
Local application of retinoic acid to the limb bond mimics the action of the polarizing region
Tickle, C. A., Alberts, B., Wolpert, L., & Lee, J. (1982) · Nature · doi:10.1038/296564a0 · Cited by 663
Absence of radius and ulna in mice lacking hoxa-11 andhoxd-11
Davis, A. P., Witte, D. P., Hsieh‐Li, H. M., Potter, S. S., & Capecchi, M. R. (1995) · Nature · doi:10.1038/375791a0 · Cited by 584
Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity
Litingtung, Y., Dahn, R. D., Li, Y., Fallon, J. F., & Chiang, C. C. (2002) · Nature · doi:10.1038/nature01033 · Cited by 579
Mutations in human TBX3 alter limb, apocrine and genital development in ulnar-mammary syndrome
Bamshad, M., Lin, R. C., Law, D. J., Watkins, W. S., Krakowiak, P. A., Moore, M. E., Franceschini, P., Lala, R., Holmes, L. B., Gebuhr, T. C., et al. (1997) · Nature Genetics · doi:10.1038/ng0797-311 · Cited by 540
Lewis, P. M., Dunn, M., McMahon, J. A., Logan, M. P. O., Martin, J. F., St‐Jacques, B., & McMahon, A. P. (2001) · Cell · doi:10.1016/s0092-8674(01)00369-5 · Cited by 515
Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod
Fromental-Ramain, C., Warott, X., Messadecq, N., LeMeur, M., Dollé, P., & Chambon, P. (1995) · Development · doi:10.1242/dev.122.10.2997 · Cited by 435
Progression of Vertebrate Limb Development Through SHH-Mediated Counteraction of GLI3
Welscher, P. T., Zúñiga, A., Kuijper, S. J. M., Drenth, T., Goedemans, H. J., Meijlink, F. C. P. W., & Zeller, R. (2002) · Science · doi:10.1126/science.1075620 · Cited by 372
Jacobs, J. J. L., Keblusek, P., Robanus-Maandag, E., Kristel, P., Lingbeek, M., Nederlof, P. M., van Welsem, T., van de Vijver, M. J., Koh, E. Y., Daley, G. Q., et al. (2000) · Nature Genetics · doi:10.1038/81583 · Cited by 368
Chapter 10 Manipulating Gene Expression with Replication--Competent Retroviruses
Morgan, B. A., & Fekete, D. M. (1996) · Methods in cell biology · doi:10.1016/s0091-679x(08)60629-9 · Cited by 343
Merino, R., Rodríguez‐León, J., Macias, D., Gañán, Y., Economides, A. N., & Hurlé, J. M. (1999) · Development · doi:10.1242/dev.126.23.5515 · Cited by 338
The T-box genes Tbx4 and Tbx5 regulate limb outgrowth and identity
Rodrı́guez-Esteban, C., Tsukui, T., Yonei‐Tamura, S., Magallon, J., Tamura, K., & Belmonte, J. C. I. (1999) · Nature · doi:10.1038/19769 · Cited by 307
Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations
Morgan, B. A., Izpisúa‐Belmonte, J. C., Duboule, D., & Tabin, C. J. (1992) · Nature · doi:10.1038/358236a0 · Cited by 302
Davenport, T. G., Jerome-Majewska, L. A., & Papaioannou, V. E. (2003) · Development · doi:10.1242/dev.00431 · Cited by 295
Gibson-Brown, J., Agulnik, S., Chapman, D. L., Alexiou, M., Garvey, N., Lee, S., & Papaioannou, V. (1996) · Mechanisms of Development · doi:10.1016/0925-4773(96)00514-x · Cited by 288
Tbx5 and Tbx4 genes determine the wing/leg identity of limb buds
Takeuchi, J., Koshiba‐Takeuchi, K., Matsumoto, K., Vogel‐Höpker, A., Naitoh-Matsuo, M., Ogura, K., Takahashi, N., Yasuda, K., & Ogura, T. (1999) · Nature · doi:10.1038/19762 · Cited by 267
Self-citationInterdigital Regulation of Digit Identity and Homeotic Transformation by Modulated BMP Signaling
Dahn, R. D., & Fallon, J. F. (2000) · Science · doi:10.1126/science.289.5478.438 · Cited by 263
Serial deletions and duplications suggest a mechanism for the collinearity of Hoxd genes in limbs
Kmita, M., Fraudeau, N., Hérault, Y., & Duboule, D. (2002) · Nature · doi:10.1038/nature01189 · Cited by 225
Drossopoulou, G. I., Lewis, K. E., Sanz‐Ezquerro, J. J., Nikbakht, N., McMahon, A. P., Hofmann, C., & Tickle, C. A. (2000) · Development · doi:10.1242/dev.127.7.1337 · Cited by 216
Involvement of T-box genes Tbx2-Tbx5 in vertebrate limb specification and development
Gibson‐Brown, J. J., Agulnik, S. I., Silver, L. M., Niswander, L. A., & Papaioannou, V. E. (1998) · Development · doi:10.1242/dev.125.13.2499 · Cited by 177
Logan, M. P. O., Simon, H., & Tabin, C. (1998) · Development · doi:10.1242/dev.125.15.2825 · Cited by 176
López-Martínez, A., Chang, D. T., Chiang, C. C., Porter, J. A., Ros, M. A., Simandl, B. K., Beachy, P. A., & Fallon, J. F. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00156-4 · Cited by 174
Lingbeek, M. E., Jacobs, J. J. L., & van Lohuizen, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200403200 · Cited by 160
Wilkinson, D. G. (1993) · doi:10.1093/oso/9780199634231.003.0026 · Cited by 153
Expression of T-box genes Tbx2–Tbx5 during chick organogenesis
Gibson‐Brown, J. J., Agulnik, S. I., Silver, L. M., & Papaioannou, V. E. (1998) · Mechanisms of Development · doi:10.1016/s0925-4773(98)00056-2 · Cited by 145
Ohuchi, H., Takeuchi, J., Yoshioka, H., Ishimaru, Y., Ogura, K., Takahashi, N., Ogura, T., & Noji, S. (1998) · Development · doi:10.1242/dev.125.1.51 · Cited by 122
Self-citationConserved and divergent expression of T-box genes Tbx2-Tbx5 in Xenopus
Takabatake, Y., Takabatake, T., & Takeshima, K. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00329-9 · Cited by 84
Murine Tbx2 contains domains that activate and repress gene transcription.
Paxton, C., Zhao, H.-H. H., Chin, Y., Langner, K., & Reecy, J. (2002) · Gene · doi:10.1016/s0378-1119(01)00878-2 · Cited by 83
Regulation of Tbx3 expression by anteroposterior signalling in vertebrate limb development.
Tümpel, S., Sanz-Ezquerro, J., Isaac, A., Eblaghie, M. C., Dobson, J., & Tickle, C. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0762 · Cited by 76
Cloning, Mapping, and Expression Analysis ofTBX15,a New Member of the T-Box Gene Family
Agulnik, S. I., Papaioannou, V. E., & Silver, L. M. (1998) · Genomics · doi:10.1006/geno.1998.5278 · Cited by 52
Caruccio, N. C., Martinez-Lopez, A., Harris, M. P., Dvorak, L., BITGOOD, J. J., Simandl, B. K., & Fallon, J. F. (1999) · Developmental Biology · doi:10.1006/dbio.1999.9321 · Cited by 48
Growth of Positive Channels in Non-uniform Fields during Impulse Breakdown
MENEMENLIS, C. (1962) · Nature · doi:10.1038/196564a0 · Cited by 9
Cited by
Sorted by citations
T-Box Genes in Vertebrate Development
Naiche, L. A., Harrelson, Z., Kelly, R. G., & Papaioannou, V. E. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.073003.105925 · Cited by 437
Wnt/β-catenin signaling is sufficient and necessary for synovial joint formationPreprint
Guo, X., Day, T. F., Jiang, X., Garrett-Beal, L. J., Topol, L. Z., & Yang, Y. (2004) · Genes & Development · doi:10.1101/gad.1230704 · Cited by 391
Harrelson, Z., Kelly, R. G., Goldin, S. N., Gibson‐Brown, J. J., Bollag, R. J., Silver, L. M., & Papaioannou, V. E. (2004) · Development · doi:10.1242/dev.01378 · Cited by 302
Uncoupling Sonic hedgehog control of pattern and expansion of the developing limb bud.
Zhu, J.-J., Nakamura, E., Nguyen, M.-T. T., Bao, X., Akiyama, H., & Mackem, S. (2008) · Developmental Cell · doi:10.1016/j.devcel.2008.01.008 · Cited by 317
Isl1Cre reveals a common Bmp pathway in heart and limb development
Yang, L., Cai, C.-L., Lin, L., Qyang, Y., Chung, C., Monteiro, R. M., Mummery, C. L., Fishman, G. I., Cogen, A., & Evans, S. (2006) · Development · doi:10.1242/dev.02322 · Cited by 267
Metadata
- Authors
- Suzuki, T., Takeuchi, J., Koshiba-Takeuchi, K., & Ogura, T.
- Affiliations
- Nara Institute of Science and Technology (JP)
- Tohoku University (JP)
- Corresponding author
- Ogura, Toshihiko
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2004-01
- Volume
- 6
- Issue
- 1
- Pages
- 43-53
- ISSN
- 1534-5807 (ISSN-L)
- OpenAlex
- W2074557542
- Cited by
- 148
- References
- 34
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2022: 3 · 2021: 13 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 2 · 2014: 7 · 2013: 7 · 2012: 10
- FWCI
- 5.33
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Ministry of Education, Culture, Sports, Science and Technology
- Korea Toray Science Foundation
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Developmental Biology › Congenital limb and hand anomalies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Hedgehog Signaling Pathway Studies
- Keywords
- TBX2, TBX3, digit identity, Sonic hedgehog signaling, BMP signaling, noggin, homeotic transformation, Hoxd genes, limb bud development
- MeSH terms
- Animals, Chick Embryo, Genes, Homeobox, Hindlimb, Mutation, Toes, Signal Transduction, Trans-Activators, Transforming Growth Factor beta, Homeodomain Proteins, Gene Expression Regulation, Developmental, Limb Buds, Bone Morphogenetic Proteins, Body Patterning, T-Box Domain Proteins, Models, Animal, Hedgehog Proteins, Bone Morphogenetic Protein 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review