Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.
Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.
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DOI：
10.1016/j.ydbio.2016.06.002
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发表时间：
2016-08-01
影响因子：
2.7
通讯作者：
Mariani FV
中科院分区：
文献类型：
--
作者：
Mah IK;Soloff R;Izuhara AK;Lakeland DL;Wang C;Mariani FV
极化上皮定义了生物体内的边界、空间和空洞。空化是一种产生多细胞空心球或管子的过程，通常与有组织的上皮细胞的形成有关。为了形成这些上皮层，细胞最终必须建立一个明显的顶端-基底端。在不同物种中，非典型的PKC被认为是顶端-基底端的极性所必需的。在这里，我们表明，虽然Prkci同工酶缺失的细胞表现出一些极性特征，但它们无法正确分离顶端-基底蛋白，形成协调的外胚层上皮，或参与正常的空化。空化失败可能是由于内部细胞过度生长或内部细胞无法死亡。然而，空细胞在增殖率上没有明显的变化，仍然能够经历细胞死亡，这表明这些过程中的变化不是空化失败的主要原因。过表达BMP4或Ezrin可能通过促进细胞死亡、极性和分化来部分挽救表型。然而，这两种方法都不足以提供产生极化上皮和完全挽救空化所需的线索。有趣的是，当野生型和Prkci−/−ES细胞混合在一起时，极化的外胚层上皮形成，空化被挽救，这可能是由于野生型细胞产生非自主极性线索的能力。我们的结论是，Prkci不是细胞对这些提示做出反应所必需的，尽管它需要产生这些提示。综上所述，这些发现表明，环境因素可以促进极化上皮的形成，空化需要多种基本细胞过程的适当协调，包括增殖、分化、细胞死亡和尖端-基底端极化。
Polarized epithelia define boundaries, spaces, and cavities within organisms. Cavitation, a process by which multicellular hollow balls or tubes are produced, is typically associated with the formation of organized epithelia. In order for these epithelial layers to form, cells must ultimately establish a distinct apical-basal polarity. Atypical PKCs have been proposed to be required for apical-basal polarity in diverse species. Here we show that while cells null for the Prkci isozyme exhibit some polarity characteristics, they fail to properly segregate apical-basal proteins, form a coordinated ectodermal epithelium, or participate in normal cavitation. A failure to cavitate could be due to an overgrowth of interior cells or to an inability of interior cells to die. Null cells however, do not have a marked change in proliferation rate and are still capable of undergoing cell death, suggesting that alterations in these processes are not the predominant cause of the failed cavitation. Overexpression of BMP4 or EZRIN can partially rescue the phenotype possibly by promoting cell death, polarity, and differentiation. However, neither is sufficient to provide the required cues to generate a polarized epithelium and fully rescue cavitation. Interestingly, when wildtype and Prkci−/− ES cells are mixed together, a polarized ectodermal epithelium forms and cavitation is rescued, likely due to the ability of wildtype cells to produce non-autonomous polarity cues. We conclude that Prkci is not required for cells to respond to these cues, though it is required to produce them. Together these findings indicate that environmental cues can facilitate the formation of polarized epithelia and that cavitation requires the proper coordination of multiple basic cellular processes including proliferation, differentiation, cell death, and apical-basal polarization.
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影响因子：
10.5
作者：
Jedrusik, Agnieszka;Parfitt, David-Emlyn;Zernicka-Goetz, Magdalena
通讯作者：
Zernicka-Goetz, Magdalena
影响因子：
3.6
作者：
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通讯作者：
Alarcon, Vernadeth B.
影响因子：
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作者：
Horne-Badovinac, S;Lin, D;Abdelilah-Seyfried, S
通讯作者：
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影响因子：
2.6
作者：
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通讯作者：
Watson, AJ
影响因子：
1.2
作者：
Fogel, Jennifer L.;Thu Zan Tun Thein;Mariani, Francesca V.
通讯作者：
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