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The regulation of epithelial proliferation during organ morphogenesis is crucial for normal development, as dysregulation is associated with tumor formation. Non-coding microRNAs (miRNAs), such as miR-200c, are post-transcriptional regulators of genes involved in cancer. However, the role of miR-200c during normal development is unknown. We screened miRNAs expressed in the mouse developing submandibular gland (SMG) and found that miR-200c accumulates in the epithelial end buds. Using both loss- and gain-of-function, we demonstrated that miR-200c reduces epithelial proliferation during SMG morphogenesis. To identify the mechanism, we predicted miR-200c target genes and confirmed their expression during SMG development. We discovered that miR-200c targets the very low density lipoprotein receptor (Vldlr) and its ligand reelin, which unexpectedly regulate FGFR-dependent epithelial proliferation. Thus, we demonstrate that miR-200c influences FGFR-mediated epithelial proliferation during branching morphogenesis via a Vldlr-dependent mechanism. miR-200c and Vldlr may be novel targets for controlling epithelial morphogenesis during glandular repair or regeneration.

The long-term environmental impact and potential human health hazards resulting from Hurricanes Katrina and Rita throughout much of the United States Gulf Coast, particularly in the New Orleans, Louisiana, USA area are still being assessed and realized after more than four years. Numerous government agencies and private entities have collected environmental samples from throughout New Orleans and found concentrations of contaminants exceeding human health screening values as established by the United States Environmental Protection Agency (USEPA) for air, soil, and water. To further assess risks of exposure to toxic concentrations of soil contaminants for citizens, particularly children, returning to live in New Orleans following the storms, soils collected from schoolyards prior to Hurricane Katrina and after Hurricane Rita were screened for 26 metals. Concentrations exceeding USEPA Regional Screening Levels (USEPA-RSL), total exposure, non-cancer endpoints, for residential soils for arsenic (As), iron (Fe), lead (Pb), and thallium (Tl) were detected in soil samples collected from schoolyards both prior to Hurricane Katrina and after Hurricane Rita. Approximately 43% (9/21) of schoolyard soils collected prior to Hurricane Katrina contained Pb concentrations greater than 400mgkg(-1), and samples from four schoolyards collected after Hurricane Rita contained detectable Pb concentrations, with two exceeding 1700mgkg(-1). Thallium concentrations exceeded USEPA-RSL in samples collected from five schoolyards after Hurricane Rita. Based upon these findings and the known increased susceptibility of children to the effects of Pb exposure, a more extensive assessment of the soils in schoolyards, public parks and other residential areas of New Orleans for metal contaminants is warranted.