Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling
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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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Critical morphogenic and oncogenic signaling pathways, including BMPs, Shh, TGF-β, FGFs, Wnt/β-catenin, and BRAF/MAPK, participate in TBX3 expression regulation, mostly at the transcriptional level.
“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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“Thus, critical morphogenic and oncogenic signaling pathways, such as BMPs 17 , Shh 18 , TGF-β 19 , FGFs 20 , Wnt/ β -catenin 21 , as well as BRAF/MAPK pathway, participate in TBX3 expression regulation, mostly at the transcriptional level 12,15 .”
BackgroundTbx2 and Tbx3 regulate cell fate progression of the otic vesicle for inner ear development
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Upstream regulation for initiation of restricted Shh expression in the chick limb bud
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- 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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