The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Abnormal gastrointestinal development in PDGF-A and PDGFR-α deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis
Abstract
Development of the gastrointestinal (GI) tract depends on reciprocal epithelial-mesenchymal cell signaling. Here, we demonstrate a role for platelet-derived growth factor-A (PDGF-A) and its receptor, PDGFR-α, in this process. Mice lacking PDGF-A or PDGFR-α were found to develop an abnormal GI mucosal lining, including fewer and misshapen villi and loss of pericryptal mesenchyme. Onset of villus morphogenesis correlated with the formation of clusters of PDGFR-α positive cells, ‘villus clusters’, which remained located at the tip of the mesenchymal core of the growing villus. Lack of PDGF-A or PDGFR-α resulted in progressive depletion of PDGFR-α positive mesenchymal cells, the formation of fewer villus clusters, and premature expression of smooth muscle actin (SMA) in the villus mesenchyme. We found that the villus clusters were postmitotic, expressed BMP-2 and BMP-4, and that their formation correlated with downregulated DNA synthesis in adjacent intestinal epithelium. We propose a model in which villus morphogenesis is initiated as a result of aggregation of PDGFR-α positive cells into cell clusters that subsequently function as mesenchymal centers of signaling to the epithelium. The role of PDGF-A seems to be to secure renewal of PDGFR-α positive cells when they are consumed in the initial rounds of cluster formation.
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Pericyte Loss and Microaneurysm Formation in PDGF-B-Deficient Mice
Lindahl, P., Johansson, B. R., Levéen, P., & Betsholtz, C. (1997) · Science · doi:10.1126/science.277.5323.242 · Cited by 2,226
Self-citationHellström, M., Kalén, M., Lindahl, P., Abramsson, A., & Betsholtz, C. (1999) · Development · doi:10.1242/dev.126.14.3047 · Cited by 1,700
Self-citationScatter factor/hepatocyte growth factor is essential for liver development
Schmidt, C., Bladt, F., Goedecke, S., Brinkmann, V., Zschiesche, W., Sharpe, M., Gherardi, E., & Birchmeler, C. (1995) · Nature · doi:10.1038/373699a0 · Cited by 1,394
Bitgood, M. J., & McMahon, A. P. (1995) · Developmental Biology · doi:10.1006/dbio.1995.0010 · Cited by 1,370
Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.
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Self-citationPlacental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor
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Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor
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Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice.
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Cited by
Regulation of PDGF and its receptors in fibrotic diseases
Bonner, J. C. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.03.006 · Cited by 768
Insight into the physiological functions of PDGF through genetic studies in mice
Betsholtz, C. (2004) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2004.03.005 · Cited by 437
Self-citationUnique and conserved aspects of gut development in zebrafish
Wallace, K. N., & Pack, M. (2003) · Developmental Biology · doi:10.1016/s0012-1606(02)00034-9 · Cited by 349
Hepatocellular carcinoma: signaling pathways and therapeutic advances
Zheng, J., Wang, S., Xia, L., Sun, Z., Chan, K. M., Bernards, R., Qin, W., Chen, J., Xia, Q., & Jin, H. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02075-w · Cited by 341
Greicius, G., Kabiri, Z., Sigmundsson, K., Liang, C., Bunte, R., Singh, M. K., & Virshup, D. M. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1713510115 · Cited by 286
Metadata
- Authors
- Karlsson, L., Lindahl, P., Heath, J. K., & Betsholtz, C.
- Venue
- Development
- Publisher
- The Company of Biologists
- Published
- 2000-08-15
- Volume
- 127
- Issue
- 16
- Pages
- 3457-3466
- ISSN
- 0950-1991 (ISSN-L)
- 1477-9129
- OpenAlex
- W2163796644
- Cited by
- 316
- References
- 44
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Abnormal gastrointestinal development in PDGF-A and PDGFR-α deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. https://app.cochat.ai/papers/10.1242/dev.127.16.3457
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- Karlsson, L., Lindahl, P., Heath, J. K., & Betsholtz, C. (2000). Abnormal gastrointestinal development in PDGF-A and PDGFR-α deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis. Development. https://doi.org/10.1242/dev.127.16.3457
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