Optic cup and lens development requires Pax6 expression in the early optic vesicle during a narrow time window
Optic cup and lens development requires Pax6 expression in the early optic vesicle during a narrow time window
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DOI：
10.1016/j.ydbio.2006.02.033
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发表时间：
2006-06-01
影响因子：
2.7
通讯作者：
Adler, Ruben
中科院分区：
文献类型：
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作者：
Canto-Soler, M. Valeria;Adler, Ruben
Pax6突变导致复杂的眼部畸形，但尚不清楚早期眼睛发育是否需要Pax6在视神经囊泡（OV）和晶状体上皮中都发挥作用，还是仅在后者中发挥作用。为了研究这个问题，我们在晶状体基板形成开始之前用抗pax6或对照的形态学对OV进行电穿孔。在抗Pax6治疗后10小时，OV中已经检测到Pax6下调，并伴有OV细胞死亡的显著增加。此后出现小眼样表型，其严重程度与发育阶段有关。当在Hamburger Hamilton (HH) 10期进行治疗时，没有视神经杯形成，尽管晶状体上皮中Pax6表达正常，但晶状体发育流产。在HH 11期处理导致晶状体和视杯结构正常，尽管后者显示出一些转录因子的异常表达域。因此，早期眼睛发育需要细胞自主Pax6功能，不仅在晶状体中，而且在视神经囊泡中，它在细胞存活中起着迄今未知的作用。此外，研究结果还表明，OV中存在一个关键阶段，在这个阶段Pax6的表达对于正常晶状体发育是必要的。(c) 2006爱思唯尔公司版权所有。
Pax6 mutations cause complex ocular malformations, but it is uncertain whether early eye development normally requires Pax6 function in both the optic vesicle (OV) and the lens epithelium, or only in the latter. To investigate this question, we electroporated the OV with anti-Pax6 or control morpholmos before the onset of lens placode formation. Pax6 downregulation was already detectable in the OV 10 h after anti-Pax6 treatment, and was accompanied by a significant increase in the death of OV cells. A small eye-like phenotype developed thereafter, whose severity was developmental stage-dependent. When treatment was applied at Hamburger Hamilton (HH) stage 10, there was no optic cup formation, and lens development was abortive despite normal Pax6 expression in the lens epithelium. Treatment at HH stage 11 resulted in structurally normal lens and optic cup, although the latter showed abnormal expression domains for several transcription factors. Early eye development therefore requires cell-autonomous Pax6 function not only in the lens but also in the optic vesicle, where it plays a hitherto unknown role in cell survival. The results, moreover, indicate that there is a critical stage during which Pax6 expression in the OV is necessary for normal lens development. (c) 2006 Elsevier Inc. All rights reserved.