The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice
Open accessAbstract
Members of the transforming growth factor (TGF)-β superfamily have been shown to play a variety of important roles in embryogenesis, including dorsal and ventral mesoderm induction. The tumor suppressor SMAD4, also known as DPC4, is believed to be an essential factor that mediates TGF-β signals. To explore functions of SMAD4 in development, we have mutated it by truncating its functional C-domain. We show that Smad4 is expressed ubiquitously during murine embryogenesis. Mice heterozygous for the Smad4 ex8/+ mutation are developmentally normal, whereas homozygotes die between embryonic day 6.5 (E6.5) and 8.5. All Smad4 ex8/ex8 mutants are developmentally delayed at E6 and show little or no elongation in the extraembryonic portion of late egg cylinder stage embryos. Consistent with this, cultured Smad4 ex8/ex8 blastocyst outgrowths suffer cellular proliferation defects and fail to undergo endoderm differentiation. Although a portion of mutant embryos at E8.5 show an increase in the embryonic ectoderm and endoderm, morphological and molecular analyses indicate that they do not form mesoderm. Altogether, these data demonstrate that SMAD4-mediated signals are required for epiblast proliferation, egg cylinder formation, and mesoderm induction.
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Cites
DPC4 , A Candidate Tumor Suppressor Gene at Human Chromosome 18q21.1
Hahn, S. A., Schutte, M., Shamsul Hoque, A. T. M., Moskaluk, C. A., da Costa, L. T., Rozenblum, E., Weinstein, C. L., Fischer, A., Yeo, C. J., Hruban, R. H., et al. (1996) · Science · doi:10.1126/science.271.5247.350 · Cited by 2,337
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Self-citationTransforming Growth Factor-β1 to the Bone
Janssens, K., ten Dijke, P., Janssens, S., & Van Hul, W. (2005) · Endocrine Reviews · doi:10.1210/er.2004-0001 · Cited by 710
Bardeesy, N., Cheng, K.-H., Berger, J. H., Chu, G. C., Pahler, J., Olson, P., Hezel, A. F., Horner, J., Lauwers, G. Y., Hanahan, D., et al. (2006) · Genes & Development · doi:10.1101/gad.1478706 · Cited by 674
Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects
Chang, H., Huylebroeck, D., Verschueren, K., Guo, Q., Matzuk, M. M., & Zwijsen, A. (1999) · Development · doi:10.1242/dev.126.8.1631 · Cited by 435
Disruption of Gastrulation and Heparan Sulfate Biosynthesis in EXT1-Deficient Mice
Lin, X., Wei, G., Shi, Z., Dryer, L., Esko, J. D., Wells, D. E., & Matzuk, M. M. (2000) · Developmental Biology · doi:10.1006/dbio.2000.9798 · Cited by 427
Metadata
- Authors
- Yang, X., Li, C., Xu, X., & Deng, C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-03-31
- Volume
- 95
- Issue
- 7
- Pages
- 3667-3672
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1980401378
- Cited by
- 361
- References
- 1
- FWCI
- 8.55
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. https://app.cochat.ai/papers/10.1073/pnas.95.7.3667
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- Yang, X., Li, C., Xu, X., & Deng, C. (1998). The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.7.3667
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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