Cited by 152Developmental Biology and Gene RegulationCongenital limb and hand anomaliesHedgehog Signaling Pathway Studies

Tbx Genes Specify Posterior Digit Identity through Shh and BMP Signaling

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Suzuki, Takayuki, Takeuchi, Jun, Koshiba-Takeuchi, Kazuko, Ogura, Toshihiko·2004·Developmental Cell

Abstract

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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Crossref · 10.1016/s1534-5807(03)00401-5

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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.”

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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
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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