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.
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“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]
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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
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Items 101–152 of 152
Sentürker, S., Thomas, J. T., Mateshaytis, J., & Moos, M. C. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039380 · Cited by 12
Dynamic expression of Tbx2 and Tbx3 in developing mouse pancreas
Begum, S., & Papaioannou, V. E. (2011) · Gene Expression Patterns · doi:10.1016/j.gep.2011.08.003 · Cited by 12
Butz, N. V., Campbell, C. E., & Gronostajski, R. M. (2004) · Gene · doi:10.1016/j.gene.2004.07.024 · Cited by 11
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Sharma, D., Mirando, A. J., Leinroth, A., Long, J. T., Karner, C. M., & Hilton, M. J. (2021) · PLOS Genetics · doi:10.1371/journal.pgen.1009982 · Cited by 10
Complex functional redundancy of Tbx2 and Tbx3 in mouse limb development
Lopatka, A., & Moon, A. (2022) · Developmental Dynamics · doi:10.1002/dvdy.484 · Cited by 7
Suzuki, T., & Fallon, J. F. (2021) · Developmental Dynamics · doi:10.1002/dvdy.323 · Cited by 8
Self-citationAtavisms in the avian hindlimb and early developmental polarity of the limb
Paese, C. L. B., Hawkins, M. B., Brugmann, S. A., & Harris, M. P. (2021) · Developmental Dynamics · doi:10.1002/dvdy.318 · Cited by 7
TBX2/3 is required for regeneration of dorsal‐ventral and medial‐lateral polarity in planarians
Tian, Q., Sun, Y., Gao, T., Li, J., Hao, Z., Fang, H., & Zhang, S. (2021) · Journal of Cellular Biochemistry · doi:10.1002/jcb.29905 · Cited by 5
Heart Development and T‐box Transcription Factors: Lessons from Avian Embryos
Shelton, E. L., & Yutzey, K. E. (2007) · Advances in developmental biology · doi:10.1016/s1574-3349(07)18003-0 · Cited by 5
A Novel Osteochondrodysplasia With Empty Sella Associates With a TBX2 Variant
Mäkitie, R. E., Toiviainen‐Salo, S., Kaitila, I., & Mäkitie, O. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.845889 · Cited by 3
16p11.2 is required for neuronal polarity
Li, Z., He, X., & Feng, J. (2013) · World Journal of Neuroscience · doi:10.4236/wjns.2013.34029 · Cited by 4
Light‐induced local gene expression in primary chick cell culture system
Kitajima, K., Kawahira, N., Lee, S., Tamura, K., Morishita, Y., & Ohtsuka, D. (2021) · Development Growth & Differentiation · doi:10.1111/dgd.12721 · Cited by 3
Tbx genes influence early gene expression and photoreceptor patterning in the chick retina
Ayten, M., Joisher, H. N. V., Prabhakara, C., & Cepko, C. L. (2026) · Developmental Biology · doi:10.1016/j.ydbio.2026.02.005 · Cited by 2
Spatiotemporal pattern of EphA4 gene expression in developing quail limb buds
Arisawa, K., Yazawa, S., EGUCHI, J., KAGAMI, H., & Ono, T. (2005) · Animal Science Journal · doi:10.1111/j.1740-0929.2005.00239.x · Cited by 2
Molecular Genetics of Human Congenital Limb Malformations
Pickering, J., & Towers, M. (2014) · Encyclopedia of Life Sciences · doi:10.1002/9780470015902.a0025686 · Cited by 2
The Growth Plate: Embryologic Origin, Structure, and Function
Frances, J., Erol, B., & Dormans, J. P. (2011) · Elsevier eBooks · doi:10.1016/b978-1-4160-3479-7.10173-9 · Cited by 2
MECANISMOS MOLECULARES QUE CONTROLAN EL DESARROLLO DE LA EXTREMIDAD DE LOS VERTEBRADOS
Abarca‐Buis, R. F., Garciadiego-Cázares, D., & Chimal‐Monroy, J. (2006) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · Cited by 1
Grigoriou, E., Trocle, A., & Dormans, J. P. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-35214-7.00140-2 · Cited by 1
Cloning and expression of Tbx3 gene in Siberian sturgeon, Acipenser baerii
ZHANG, H., Fan, C., & Song, J. (2013) · Zoological Research · doi:10.3724/sp.j.1141.2012.02158 · Cited by 1
Mathieu, Y. (2006) · edoc (University of Basel) · doi:10.5451/unibas-004215017 · Cited by 1
Studying enhancer function using the Tbx4 locus as a model
Mihala, A. G. (2014) · Cited by 1
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Sharma, D., Mirando, A. J., Leinroth, A. P., Long, J. T., Karner, C. M., & Hilton, M. J. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.17.158501 · Cited by 1
Wehn, A. K. (2010) · D-Scholarship@Pitt (University of Pittsburgh)
Regulação do gene TBX3 por TGF-b1 em células mesangiais.
Wensing, L. A. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2013.tde-12062013-103546
Monogenic Traits Associated with Structural Variants in Chicken and Horse
Imsland, F. (2015) · Uppsala University Publications (Uppsala University)
3D gene expression patterns, tissue anatomy and fate map of the developing chick wing
Downie, H. F. (2009) · The University of Bath Online Publications Store (The University of Bath)
Erson, A., & Petty, E. (2011) · Atlas of Genetics and Cytogenetics in Oncology and Haematology · doi:10.4267/2042/38243
Chisholm, R. H., Hughes, B. D., Landman, K. A., & Hutson, J. M. (2013) · Journal of Pediatric Surgery · doi:10.1016/j.jpedsurg.2012.08.034
Roles of Irx3/5 in Mouse Hindlimb Development
Li, D. (2013) · TSpace (University of Toronto)
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Richmond, N. (2016) · Scholarship@Western (Western University)
The Role of Iroquois 3 and 5 in Limb Bud Pattern Formation and Morphogenesis
Li, D. (2014) · TSpace (University of Toronto)
Alexandra, S., Pascoal, R., & Palmeirim, D. I. (2006)
The T-box transcription factor Tbx15 is required for skeletal development
Singh, M., Petry, M., Haenig, B., Lescher, B., Leitges, M., & Kispert, A. (2005) · Max Planck Institute for Plasma Physics
Secondary Smad1/5/8-Dependent Signaling Downstream of SHH Determines Digit Identity
Suzuki, T. (2014) · Springer eBooks · doi:10.1007/978-4-431-54634-4_12
Self-citationWolpert, L., Tickle, C. A., Arias, A. M., Lawrence, P. A., Lumsden, A., Robertson, E. J., & Smith, J. (2017) · Dunod eBooks · doi:10.3917/dunod.wolpe.2017.01.0446
Ferretti, P., & Tickle, C. A. (2008) · Wiley eBooks · doi:10.1002/9780470090121.ch7
Mamoor, S. (2020) · OSF Preprints (OSF Preprints) · doi:10.31219/osf.io/5dhyp
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435297
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435294
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435303
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435300
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435306
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435318
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435312
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435309
Lüdtke, T. H., Wojahn, I., Kleppa, M.-J., Schierstaedt, J., Christoffels, V. M., Künzler, P., & Kispert, A. (2021) · Figshare · doi:10.6084/m9.figshare.14235003
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435315
Wang, Z., Dong, D., Ru, B., Young, R. L., Han, N., Guo, T., & Zhang, S. Y. (2021) · Figshare · doi:10.6084/m9.figshare.14435321
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Tang, Y., Bai, S., Li, S., Mao, Y., Dang, W., Xue, H., Shang, S., Jia, Z., Li, X., Liu, Y., et al. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2605261123
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Francis, N. (2011) · OpenCommons - UConn (University of Connecticut)
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
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