Two nested developmental waves demarcate a compartment boundary in the mouse lung.
Two nested developmental waves demarcate a compartment boundary in the mouse lung.
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DOI：
10.1038/ncomms4923
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发表时间：
2014-05-29
影响因子：
16.6
通讯作者：
Chen, Jichao
中科院分区：
文献类型：
--
作者：
Alanis, Denise Martinez;Chang, Daniel R.;Akiyama, Haruhiko;Krasnow, Mark A.;Chen, Jichao
肺是一个分支管状网络，具有两个不同的部分——近端传导气道和外周气体交换区域，它们由一个被称为支气管肺泡导管连接处（BADJ）的明确边界分隔开来。在此，我们对发育中的小鼠肺进行三维成像，并表明在一种全身性激素信号的控制下，两次嵌套的发育波勾勒出了BADJ。第一次分支形态发生波在整个胚胎发育过程中推进，为两个部分都产生分支。第二次传导气道分化波跟随第一次波，但更早终止，确定了近端部分并设定了BADJ。第二次波因糖皮质激素信号传导而终止：糖皮质激素信号传导的过早激活或缺失分别导致BADJ位置向近端或远端偏移。这些结果展示了复杂的三维器官中边界形成的一种新机制，并为早产儿肺部缺陷的糖皮质激素疗法提供了新的见解。
The lung is a branched tubular network with two distinct compartments — the proximal conducting airways and the peripheral gas exchange region — separated by a discrete boundary termed the bronchoalveolar duct junction (BADJ). Here we image the developing mouse lung in three dimensions and show that two nested developmental waves demarcate the BADJ under the control of a global hormonal signal. A first wave of branching morphogenesis progresses throughout embryonic development, generating branches for both compartments. A second wave of conducting airway differentiation follows the first wave but terminates earlier, specifying the proximal compartment and setting the BADJ. The second wave is terminated by a glucocorticoid signaling: premature activation or loss of glucocorticoid signaling causes a proximal or distal shift, respectively, in BADJ location. The results demonstrate a novel mechanism of boundary formation in complex, three-dimensional organs and provide new insights into glucocorticoid therapies for lung defects in premature birth.
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