AP-2α is required after lens vesicle formation to maintain lens integrity.
AP-2α is required after lens vesicle formation to maintain lens integrity.
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DOI：
10.1002/dvdy.24141
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
West-Mays JA
中科院分区：
文献类型：
--
作者：
Kerr CL;Zaveri MA;Robinson ML;Williams T;West-Mays JA
转录因子在调节晶状体发育中起着至关重要的作用。AP-2转录因子家族在细胞分化、细胞生长和凋亡以及晶状体和眼睛发育中起作用。AP-2α在晶状体早期发育中尤为重要，如果在基位阶段有条件地缺失，晶状体囊泡与外胚层表面的分离就会出现缺陷。AP-2α在晶状体发育后期的作用尚不清楚。为了解决这个问题，使用MLR10-Cre转基因从胚胎日(E) 10.5开始从晶状体上皮中删除AP-2α。晶状体囊泡分离后AP-2α的缺失导致形态学缺陷从E18.5开始。到P4时，MLR10-AP-2α突变体中可见一个具有多层上皮的高度空泡化的小晶体。上皮细胞呈细长状，表达纤维细胞特异性βB1和γ-结晶蛋白。上皮细胞极性和晶状体细胞粘附被破坏，并伴有ZO-1、N-Cadherin和β-catenin的错误表达。在出生后第14天至第30天，突变体晶状体上皮中观察到细胞死亡，这与上皮内细胞排列的改变有关。我们的研究结果表明，在晶状体囊泡分离后，AP-2α仍然需要维持正常的晶状体上皮细胞表型和整体晶状体完整性，并确保正确的纤维细胞分化。
Transcription factors are critical in regulating lens development. The AP-2 family of transcription factors functions in differentiation, cell growth and apoptosis, and in lens and eye development. AP-2α, in particular, is important in early lens development, and when conditionally deleted at the placode stage defective separation of the lens vesicle from the surface ectoderm results. AP-2α’s role during later stages of lens development is unknown. To address this, the MLR10-Cre transgene was used to delete AP-2α from the lens epithelium beginning at embryonic day (E) 10.5. The loss of AP-2α after lens vesicle separation resulted in morphological defects beginning at E18.5. By P4, a small highly vacuolated lens with a multilayered epithelium was evident in the MLR10-AP-2α mutants. Epithelial cells appeared elongated and expressed fiber cell specific βB1 and γ-crystallins. Epithelial cell polarity and lens cell adhesion was disrupted and accompanied by the misexpression of ZO-1, N-Cadherin, and β-catenin. Cell death was observed in the mutant lens epithelium between postnatal day (P) 14 and P30, and correlated with altered arrangements of cells within the epithelium. Our findings demonstrate that AP-2α continues to be required after lens vesicle separation to maintain a normal lens epithelial cell phenotype and overall lens integrity and to ensure correct fiber cell differentiation.
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影响因子：
2.7
作者：
Dawes, L. J.;Sugiyama, Y.;Lovicu, F. J.;Harris, C. G.;Shelley, E. J.;McAvoy, J. W.
通讯作者：
McAvoy, J. W.
影响因子：
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作者：
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Sucov, HM
影响因子：
4.4
作者：
Hsu, Cheng-Da;Kymes, Steven;Petrash, J. Mark
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Petrash, J. Mark
影响因子：
10.5
作者：
Ashery-Padan, R;Marquardt, T;Gruss, P
通讯作者：
Gruss, P
影响因子：
12.3
作者：
Eckert D;Buhl S;Weber S;Jäger R;Schorle H
通讯作者：
Schorle H