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Cited by 316

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

Karlsson, Linda, Lindahl, Per, Heath, John K., Betsholtz, Christer·2000·Development
DOI 10.1242/dev.127.16.3457
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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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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
DOI
10.1242/dev.127.16.3457
OpenAlex
W2163796644
Cited by
316
References
44
FWCI
7.05
Type
journal article
Language
en
Open access
closed

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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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