Pax2 coordinates epithelial morphogenesis and cell fate in the inner ear.
Pax2 coordinates epithelial morphogenesis and cell fate in the inner ear.
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DOI：
10.1016/j.ydbio.2010.07.007
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发表时间：
2010-09-15
影响因子：
2.7
通讯作者：
Streit A
中科院分区：
文献类型：
--
作者：
Christophorou NA;Mende M;Lleras-Forero L;Grocott T;Streit A
脊椎动物眼睛、耳朵和鼻子的重要组成部分是由表面上皮的离散斑块（称为基板）发育而来，这些斑块折叠成球体并经历复杂的形态发生。关于细胞和组织形状的变化如何与细胞命运的获得相协调，人们知之甚少。在这里，我们探讨这些过程是否受到发育中耳朵中常见转录机制的调节。规范化后，内耳前体伸长形成基板，基板内陷并转变为成人耳朵的复杂结构。我们发现转录因子 Pax2 在协调耳命运和基板形态发生中起着关键作用，但似乎独立调节每个过程。在 Pax2 缺失的情况下，耳祖细胞不仅失去耳标记物的表达，而且由于顶端定位的 N-钙粘蛋白和 N-CAM 的缺失而无法伸长。在缺乏 N-钙粘蛋白或 N-CAM 的情况下，耳细胞会失去顶端细胞与细胞的接触及其上皮形状。虽然 Pax2 的错误表达会导致两个粘附分子的异位激活，但这不足以赋予耳同一性。这些观察结果表明，Pax2 独立于细胞身份控制细胞形状，因此充当这些过程的协调员。
Crucial components of the vertebrate eye, ear and nose develop from discrete patches of surface epithelium, called placodes, which fold into spheroids and undergo complex morphogenesis. Little is known about how the changes in cell and tissue shapes are coordinated with the acquisition of cell fates. Here we explore whether these processes are regulated by common transcriptional mechanisms in the developing ear. After specification, inner ear precursors elongate to form the placode, which invaginates and is transformed into the complex structure of the adult ear. We show that the transcription factor Pax2 plays a key role in coordinating otic fate and placode morphogenesis, but appears to regulate each process independently. In the absence of Pax2, otic progenitors not only lose otic marker expression, but also fail to elongate due to the loss of apically localised N-cadherin and N-CAM. In the absence of either N-cadherin or N-CAM otic cells lose apical cell–cell contact and their epithelial shape. While misexpression of Pax2 leads to ectopic activation of both adhesion molecules, it is not sufficient to confer otic identity. These observations suggest that Pax2 controls cell shape independently from cell identity and thus acts as coordinator for these processes.
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影响因子：
2.7
作者：
Dude, Carolynn M.;Kuan, C. -Y. Kelly;Bradshaw, James R.;Greene, Nicholas D. E.;Relaix, Frederic;Stark, Michael R.;Baker, Clare V. H.
通讯作者：
Baker, Clare V. H.
影响因子：
19
作者：
D'Souza-Schorey, C
通讯作者：
D'Souza-Schorey, C
影响因子：
7
作者：
Fan, Y;Linardopoulou, E;Trask, BJ
通讯作者：
Trask, BJ
影响因子：
1.6
作者：
Christ, S;Biebel, UW;Smolders, JWT
通讯作者：
Smolders, JWT
影响因子：
--
作者：
Hans, Stefan;Christison, Joe;Westerfield, Monte
通讯作者：
Westerfield, Monte