Our proposal focuses on the localization, migration and mechanism of differentiation of the smooth muscle progenitor cells during embryonic lung development. Fibroblast Growth factor 10 is one of the earliest genes expressed in a regionalized manner in the distal mesenchyme of the embryonic lung. Our preliminary data indicate that FGF10 plays a role in myogenesis. We therefore propose to test the following Hypothesis: progenitor cells are present in the distal mesenchyme in the embryonic lung and Fgf10 can be used as a marker to characterize them. In addition, FGF10 is involved, directly or indirectly, to maintain the smooth muscle progenitor cell population and/or to allow, via BMP4, proper differentiation of these progenitors into smooth muscle cells.
Aim 1 : To determine temporal-spatial expression of LacZ and Fgf10 in a novel Fgf10-enhancer trap mouse transgenic line.
Aim 2 : To determine the migration of distal mesenchymal cells toward the distal epithelium and the expression of smooth muscle cell differentiation markers in these cells.
Aim 3 : To determine the role of Fgf10 in the maintenance and/or differentiation of smooth muscle progenitor cells in the embryonic lung.
Aim 4 : To determine the role of Bone Morphogenetic Protein 4, a downstream epithelial target of FGF10, in controlling smooth muscle progenitor cell differentiation. Health relevance: Abnormal proliferation of the smooth muscle cells around the bronchi has been shown in several human chronic diseases such as asthma, broncho-pulmonary dysplasia and lymphangioleiomyomatosis. Our proposal may identify novel targets to control the proliferation of smooth muscle.
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