Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage
Fgf10 expression identifies parabronchial smooth muscle cell progenitors and is required for their entry into the smooth muscle cell lineage
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DOI：
10.1242/dev.01795
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发表时间：
2005-05-01
期刊：
影响因子：
4.6
通讯作者：
Bellusci, S
中科院分区：
文献类型：
--
作者：
Mailleux, AA;Kelly, R;Bellusci, S
肺间质中的谱系形成知之甚少。使用转基因小鼠系表达LacZ的FGF 10调控序列的控制下，我们表明，在远端肺间充质中的FGF 10阳性细胞池包含支气管平滑肌细胞的祖细胞。在该转基因系中，Fgf 10基因表达被轻微抑制。这使我们能够通过在杂合Fgf 10背景中表达LacZ转基因来创建亚纯型Fgf 10表型。低形态Fgf 10突变型肺显示支气管上皮周围β-半乳糖苷酶阳性细胞减少，这与β-半乳糖苷酶表达细胞在远端间充质中蓄积有关。这与平滑肌肌动蛋白表达的显著减少相关，从而证明FGF 10是间充质细胞进入支气管旁平滑肌细胞谱系所主要需要的。外源性FGF 10在肺间充质培养物中不能磷酸化其已知的下游靶ERK和AKT，这强烈表明FGF 10通过上皮中间体间接作用于祖细胞群。我们提供支持的作用，上皮骨形成蛋白4介导支气管平滑肌细胞的形成。
Lineage formation in the lung mesenchyme is poorly understood. Using a transgenic mouse line expressing LacZ under the control of Fgf10 regulatory sequences, we show that the pool of Fgf10-positive cells in the distal lung mesenchyme contains progenitors of the parabronchial smooth muscle cells. Fgf10 gene expression is slightly repressed in this transgenic line. This allowed us to create a hypomorphic Fgf10 phenotype by expressing the LacZ transgene in a heterozygous Fgf10 background. Hypomorphic Fgf10 mutant lungs display a decrease in beta-galactosidase-positive cells around the bronchial epithelium associated with an accumulation of beta-galactosidase-expressing cells in the distal mesenchyme. This correlates with a marked reduction of a smooth muscle actin expression, thereby demonstrating that FGF10 is mostly required for the entry of mesenchymal cells into the parabronchial smooth muscle cell lineage. The failure of exogenous FGF10 to phosphorylate its known downstream targets ERK and AKT in lung mesenchymal cultures strongly suggests that FGF10 acts indirectly on the progenitor population via an epithelial intermediate. We provide support for a role of epithelial BMP4 in mediating the formation of parabronchial smooth muscle cells.