GATA-6 is required for maturation of the lung in late gestation
GATA-6 is required for maturation of the lung in late gestation
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DOI：
10.1152/ajplung.00044.2002
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发表时间：
2002-08-01
影响因子：
4.9
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
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作者：
Liu, C;Morrisey, EE;Whitsett, JA
GATA-6是锌指蛋白GATA家族的一员，是已知唯一在发育中的气道上皮上皮细胞中表达的家族成员。为了确定GATA-6在肺形态发生中的作用，我们在强力霉素诱导的转基因控制下，在小鼠中有条件地表达了一个含有GATA-6和强转录抑制剂的嵌合融合蛋白。多西环素处理后，GATA-6-engrailed在胚胎期(E) 6-7开始表达。虽然近端气道的分支形态形成正常进行到E16.5，但通常在出生前发生的末端气道和肺泡成熟受到抑制。e17.5 ~ 18.5时，I型细胞的水通道蛋白-5 mRNA和I型细胞标记物- α染色均降低。在gata -6基因表达后，肺外周可见甲状腺转录因子-1均匀分布，表面活性蛋白表达降低，外周气道壁变薄延迟，上皮细胞无鳞状分化。GATA-6的活性是出生前气体交换区成熟所必需的。
GATA-6, a member of the GATA family of zinc finger proteins, is the only family member known to be expressed in the epithelial cells of the developing airway epithelium. To determine the role of GATA-6 in lung morphogenesis, a chimeric fusion protein containing GATA-6 and the strong transcriptional inhibitor, engrailed, was conditionally expressed in mice under control of a doxycycline-inducible transgene. Expression of GATA-6-engrailed was initiated at embryonic day (E) 6-7 by treatment of the dam with doxycycline. Although branching morphogenesis of the proximal airways proceeded normally to E16.5, maturation of terminal airways and alveoli that normally occurs before birth was inhibited. At E17.5-18.5, aquaporin-5 mRNA and type I cell marker-alpha staining, both markers of type I cells, were decreased. Homogenous distribution of the thyroid transcription factor-1, decreased expression of surfactant proteins, delayed thinning of the walls of the peripheral airways, and lack of squamous differentiation of epithelial cells were observed in the lung periphery after expression of GATA-6-engrailed. Activity of GATA-6 is required for maturation of the gas exchange area before birth.