Abstract
Purpose: :
Our previous studies have shown that lens-specific expression of fibroblast growth factor 10 (FGF10) in transgenic mice is sufficient to induce the overlying corneal epithelial cells to differentiate into lacrimal glands. In addition, we have also shown that FGF10 expressed in the mesenchymal cells of the ocular (lacrimal and Harderian) gland rudiments is necessary for glandular differentiation. The purpose of this study was to analyze the role of Sproutys, negative feedback inhibitors of FGF and other receptor tyrosine kinase signaling, during corneal and ocular gland development.
Methods: :
Expression of Spry1, 2 and 4 in the wild type and FGF10 transgenic mice was examined by in situ hybridizations. In order to investigate the role of Sprouty during early ocular development, transgenic mice that express Spry2 in their corneal and glandular epithelial precursors were generated. Ocular development of wild type and transgenic mice was analyzed by standard histological techniques, in situ hybridization and immunohistochemistry.
Results: :
During early glandular development, endogenous expression of Spry1 and 2 was localized to the epithelial cells and Spry4 expression was predominantly in the mesenchymal cells of the glandular rudiment. In the cornea, Spry 1, 2 and 4 were not expressed in the epithelial cells but Spry1 expression was seen in the stromal cells. Expression of Spry1, 2 and 4 was upregulated in the ectopic glands that form in the corneas of transgenic mice that express FGF10 in their lens fibers. Transgenic mice that express Spry2 in their glandular epithelial precursors lack both lacrimal and Harderian glands.
Conclusions: :
Our data suggests that Sprys are potential targets of FGF10 during gland induction. The loss of lacrimal and Harderian gland rudiments in Spry2 gain-of-function mice imply that Spry2 is likely to play a negative role during glandular development. These results taken together suggest the possibility that Spry is an important downstream target and antagonist of FGF10 signaling during early glandular differentiation. These results are consistent with the role of Spry in regulation of differentiation of other organ rudiments that undergo branching morphogenesis including lungs and kidneys.
Keywords: lacrimal gland • signal transduction • transgenics/knock-outs