T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung
T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung
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DOI：
10.1002/dvdy.10208
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发表时间：
2003-01-01
影响因子：
2.5
通讯作者：
Gilbert, SF
中科院分区：
文献类型：
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作者：
Cebra-Thomas, JA;Bromer, J;Gilbert, SF
在形态发生过程中，信号通路的调控是间充质组织和上皮组织之间协调诱导的先决条件。已知间充质FGF10是一种重要的旁分泌因子，调节支气管上皮的分支形态发生。通过使用反义寡核苷酸(AS ODN)和胚胎肺的体外培养，我们证明了转录因子Tbx4和Tbx5对间充质FGF10的表达起关键作用。用针对Tbx4和Tbx5的反义寡核苷酸处理胚胎肺培养物，可降低这些转录本的水平，抑制间充质中Fgf10的表达，并完全消除新的肺分支的形成。如果局部替换FGF10作为ODN治疗的肺，上皮分支就会恢复。这些研究提供了证据，证明肺间充质产生的分支信号是由T-box基因介导的。
The regulation of signaling pathways is a prerequisite for coordinating the induction between mesenchymal and epithelial tissues during morphogenesis. Mesenchymal FGF10 is known to be an important paracrine factor regulating the branching morphogenesis of the bronchial epithelium. By using antisense oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the expression of mesenchymal FGF10. Treatment of embryonic lung cultures with AS ODNs to Tbx4 and Tbx5 reduces the level of these transcripts, suppresses Fgf10 expression in the mesenchyme, and completely eliminates the formation of new lung branches. If FGF10 is locally replaced in these AS ODN-treated lungs, epithelial branching is restored. These studies provide evidence that the production of branching signals by the lung mesenchyme is mediated by T-box genes.