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
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Absence of radius and ulna in mice lacking hoxa-11 andhoxd-11
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Shh and Gli3 are dispensable for limb skeleton formation but regulate digit number and identity
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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
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Hoxa-13 and Hoxd-13 play a crucial role in the patterning of the limb autopod
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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
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