AI Article Synopsis
- The study investigates how blood vessel development (vasculature) influences the formation of epithelial structures in the submandibular salivary gland during organ growth and healing, highlighting its potential for organ restoration.
- Researchers found that signaling through VEGFR2, a receptor on endothelial cells, is essential for the proper patterning of the salivary gland epithelium and used various experimental techniques to establish this connection.
- When endothelial cells were removed or their signaling inhibited, there was abnormal development in the gland, but adding back endothelial cells or specific mesenchymal factors helped restore normal epithelial growth and prevented early differentiation.
Article Abstract
Perfusion-independent regulation of epithelial pattern formation by the vasculature during organ development and regeneration is of considerable interest for application in restoring organ function. During murine submandibular salivary gland development, the vasculature co-develops with the epithelium during branching morphogenesis; however, it is not known whether the vasculature has instructive effects on the epithelium. Using pharmacological inhibitors and siRNA knockdown in embryonic organ explants, we determined that VEGFR2-dependent signaling is required for salivary gland epithelial patterning. To test directly for a requirement for endothelial cells in instructive epithelial patterning, we developed a novel ex vivo cell fractionation/reconstitution assay. Immuno-depletion of CD31 endothelial cells in this assay confirmed a requirement for endothelial cells in epithelial patterning of the gland. Depletion of endothelial cells or inhibition of VEGFR2 signaling in organ explants caused an aberrant increase in cells expressing the ductal proteins K19 and K7, with a reduction in Kit progenitor cells in the endbuds of reconstituted glands. Addition of exogenous endothelial cells to reconstituted glands restored epithelial patterning, as did supplementation with the endothelial cell-regulated mesenchymal factors IGFBP2 and IGFBP3. Our results demonstrate that endothelial cells promote expansion of Kit progenitor cells and suppress premature ductal differentiation in early developing embryonic submandibular salivary gland buds.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394760 | PMC |
| http://dx.doi.org/10.1242/dev.142497 | DOI Listing |
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