Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos
Open accessAbstract
Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar-mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development. We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently. Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8 and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17 in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse embryos, at a stage just prior to mammary bud initiation, induce expression of Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead. Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and Lef1 expression, supporting the idea that FGFR1 signalling is required for ear…
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Tbx3 acts as a target of Wnts in other contexts.
“These findings agree with Tbx3 acting as a target of Wnts in other contexts (25, 27–30).”
From Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade (2022) · cites this paper as [29]
Tbx3 is a target of Wnt signaling in the liver.
“We verified that Tbx3 is a target of Wnt signaling in the liver, by either over-activating or eliminating the Wnt pathway in the tissue (Figure .1A, arrows point to TBX3 + Apc KO cells, arrowheads point to TBX3 -Wls KO cells), in agreement with data from other contexts”
From Hepatocyte Cell Cycle Progression Depends on a Transcriptional Repressor Cascade Downstream of Wnt Signaling (2021) · cites this paper as Eblaghie et al. 2004
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Renard, C.-A., Labalette, C., Armengol, C., Cougot, D., Wei, Y., Cairo, S., Pineau, P., Neuveut, C., de Reyniès, A., Dejean, A., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2344 · Cited by 157 · see citing works
“February 1, 2007 908 www.aacrjournals.org effect of Wnt and fibroblast growth factor signals in mammary gland initiation ( 39 ).”
BackgroundThe roles and regulation of TBX3 in development and disease
Khan, S. F., Damerell, V., Omar, R., Du Toit, M., Khan, M., Maranyane, H. M., Mlaza, M., Bleloch, J., Bellis, C., Sahm, B. D. B., et al. (2020) · Gene · doi:10.1016/j.gene.2019.144223 · Cited by 99 · see citing works
Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade
Jin, Y., Anbarchian, T., Wu, P., Sarkar, A., Fish, M., Peng, W. C., & Nusse, R. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2203849119 · Cited by 26 · see citing works
TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration
Melzer, M. K., Schirge, S., Gout, J., Arnold, F., Srinivasan, D., Burtscher, I., Allgöwer, C., Mulaw, M., Zengerling, F., Günes, C., et al. (2023) · BMC Biology · doi:10.1186/s12915-023-01553-x · Cited by 5 · see citing works
Jin, Y., Anbarchian, T., Wu, P., Sarkar, A., Fish, M., & Nusse, R. (2021) · doi:10.1101/2021.10.15.464616 · Cited by 2 · see citing works
- Authors
- Eblaghie, M. C., Song, S., Kim, J., Akita, K., Tickle, C., & Jung, H.
- Affiliations
- University of Dundee (GB)
- Yonsei University (KR)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Tickle, Cheryll
- Jung, Han‐Sung
- Venue
- Journal of Anatomy
- Publisher
- Wiley
- Published
- 2004-07
- Volume
- 205
- Issue
- 1
- Pages
- 1-13
- ISSN
- 0021-8782 (ISSN-L)
- 1469-7580
- OpenAlex
- W2024400655
- Cited by
- 121
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 10 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 7 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 10
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Journal of Anatomy (publishedVersion)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- TBX3, Wnt signaling, FGF signaling, FGFR1, LEF1, ulnar-mammary syndrome, FGF8, FGF9, FGF4, FGF17, SU5402, signaling crosstalk, mouse embryo
- MeSH terms
- Animals, DNA-Binding Proteins, Female, Fibroblast Growth Factors, Male, Mammary Glands, Animal, Mice, Inbred Strains, Organ Culture Techniques, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Pyrroles, Transcription Factors, Signal Transduction, Protein Tyrosine Phosphatases, In Situ Hybridization, Receptors, Fibroblast Growth Factor, Gene Expression Regulation, Developmental, Receptor Protein-Tyrosine Kinases, T-Box Domain Proteins, Wnt Proteins, Mice, Receptor, Fibroblast Growth Factor, Type 1, Fibroblast Growth Factor 4, Fibroblast Growth Factor 8, Fibroblast Growth Factor 9, Lymphoid Enhancer-Binding Factor 1, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Dual Specificity Phosphatase 6
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