The requirement of Pax6 for postnatal eye development: Evidence from experimental mouse chimeras
The requirement of Pax6 for postnatal eye development: Evidence from experimental mouse chimeras
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DOI：
10.1167/iovs.06-1482
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发表时间：
2007-07-01
影响因子：
4.4
通讯作者：
Swanson, Douglas J.
中科院分区：
文献类型：
--
作者：
Li, Shengxiu;Goldowitz, Dan;Swanson, Douglas J.
目的.小眼鼠突变体（Sey）是由Pax 6基因突变引起的。以前的研究，其中使用聚集嵌合体，已经证明，Sey/Sey细胞有助于不良的神经视网膜形成小团块的细胞限制在内部视网膜在胚胎天16.5。此外，在胚胎期和出生后，透镜上皮中不存在Sey/+细胞。本研究旨在确定这些Sey/Sey和Sey/+细胞在嵌合小鼠眼中继续发育的命运。从出生后0 ~ 10天观察嵌合体眼内杂合子和纯合子Sey细胞。在Sey/Sey野生型（wt）嵌合体中，所有源自视网膜祖细胞的Sey/Sey细胞在围产期死亡。神经视网膜中仅存的Sey/Sey细胞与血管相关，包括血管内皮细胞、周细胞、星形胶质细胞和小胶质细胞，它们具有视网膜外起源。相反，Sey/+细胞形成所有视网膜细胞类别。如前所述，透镜和角膜上皮中不存在Sey/Sey细胞。然而，与以往报道不同的是，Sey/+细胞在透镜上皮和角膜组织中均有分布，而在视网膜前色素上皮中不存在Sey/Sey细胞。所有证据都表明，当Pax 6在发育的初始阶段缺失时，即使野生型细胞可提供正常的环境线索，对神经视网膜有贡献的Sey/Sey细胞也会死亡。
PURPOSE. The small eye mouse mutant (Sey) is caused by a mutation of the Pax6 gene. Previous studies, in which aggregation chimeras were used, have demonstrated that Sey/Sey cells contribute poorly to the neural retina forming small clumps of cells restricted to the inner retina at embryonic day 16.5. In addition, Sey/+ cells are absent from the lens epithelium during this embryonic period and postnatally. This study was conducted to determine the fates of these Sey/Sey and Sey/+ cells with continued development in chimeric mouse eyes.METHODS. Observations were made on heterozygous and homozygous Sey cells in chimeric eyes from postnatal day (P)0 to P10.RESULTS. In Sey/Sey wild-type (wt) chimeras, all Sey/Sey cells originating from retinal progenitor cells died at perinatal times. The only remaining Sey/Sey cells in the neural retina were associated with blood vessels, including vascular endothelial cells, pericytes, astrocytes, and microglia, which have extraretinal origins. In contrast, Sey/+ cells formed all retinal cell classes. As previously reported, Sey/Sey cells were absent from the lens and corneal epithelium. However, in contrast to previous reports, Sey/+ cells contributed to the lens epithelium as well as corneal tissues, and Sey/Sey cells were absent from the anterior retinal pigment epithelium.CONCLUSIONS. All evidence showed that, when Pax6 is absent at the initial stages of the development, Sey/Sey cells that contribute to the neural retina die, even when wild-type cells are available to provide normal environmental cues.