Minoo P, Hamdan H, Bu D, Warburton D, Stepanik P, deLemos R
Department of Pediatrics, Women's and Children's Hospital, University of Southern California School of Medicine, Los Angeles 90033, USA.
Dev Biol. 1995 Dec;172(2):694-8. doi: 10.1006/dbio.1995.8080.
TTF-1 is a homeodomain transcriptional factor expressed in thyroid, lung, and parts of the brain. In vitro, TTF-1 can activate the promoter of thyroid- and pulmonary-specific genes. We postulated that TTF-1 not only is essential for the activation of tissue-specific genes, but also may directly participate in epithelial cell morphogenesis. To test this postulate, we used an antisense oligonucleotide inhibitory strategy in an in vitro model of embryonic mouse lung branching morphogenesis. This strategy suppressed TTF-1 translation and inhibited lung branching morphogenesis. The resulting abnormal phenotype was characterized by hyperplastic and unorganized proliferation of epithelial cells in the airways. The mesenchymal compartment of the lung appeared to be unaffected. These results demonstrate, for the first time, that the expression of a homeoprotein transcriptional regulator is necessary for lung epithelial morphogenesis.
甲状腺转录因子-1（TTF-1）是一种在甲状腺、肺和部分脑区表达的同源结构域转录因子。在体外，TTF-1可激活甲状腺和肺特异性基因的启动子。我们推测TTF-1不仅对组织特异性基因的激活至关重要，还可能直接参与上皮细胞形态发生。为验证这一推测，我们在胚胎小鼠肺分支形态发生的体外模型中采用了反义寡核苷酸抑制策略。该策略抑制了TTF-1的翻译并抑制了肺分支形态发生。所产生的异常表型的特征是气道上皮细胞增生且无序增殖。肺的间充质部分似乎未受影响。这些结果首次证明，一种同源蛋白转录调节因子的表达对于肺上皮形态发生是必需的。
