Sehgal Rachna, Karcavich Rachel, Carlson Scott, Belecky-Adams Teri L
Department of Biology and Center for Regenerative Biology and Medicine, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Dev Biol. 2008 Jul 1;319(1):23-33. doi: 10.1016/j.ydbio.2008.03.041. Epub 2008 Apr 11.
Pax2 is essential for the development of the urogenital system, neural tube, otic vesicle, optic cup and optic tract [Dressler, G.R., Deutsch, U., et al., 1990. PAX2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109 (4), 787-795; Nornes, H.O., Dressler, G.R., et al., 1990. Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development 109 (4), 797-809; Eccles, M.R., Wallis, L.J., et al., 1992. Expression of the PAX2 gene in human fetal kidney and Wilms' tumor. Cell Growth Differ 3 (5), 279-289]. Within the visual system, a loss-of-function leads to lack of choroid fissure closure (known as a coloboma), a loss of optic nerve astrocytes, and anomalous axonal pathfinding at the optic chiasm [Favor, J., Sandulache, R., et al., 1996. The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. Proc. Natl. Acad. Sci. U. S. A. 93 (24), 13870-13875; Torres, M., Gomez-Pardo, E., et al., 1996. Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122 (11), 3381-3391]. This study is directed at determining the effects of ectopic Pax2 expression in the chick ventral optic cup past the normal developmental period when Pax2 is found. In ovo electroporation of Pax2 into the chick ventral optic cup results in the formation of colobomas, a condition typically associated with a loss of Pax2 expression. While the overexpression of Pax2 appears to phenocopy a loss of Pax2, the mechanism of the failure of choroid fissure closure is associated with a cell fate switch from ventral retina and retinal pigmented epithelium (RPE) to an astrocyte fate. Further, ectopic expression of Pax2 in RPE appears to have non-cell autonomous effects on adjacent RPE, creating an ectopic neural retina in place of the RPE.
Pax2对于泌尿生殖系统、神经管、耳泡、视杯和视束的发育至关重要[德雷斯勒，G.R.，多伊奇，U.等，1990年。PAX2，一种新的含小鼠配对盒基因及其在发育中的排泄系统中的表达。《发育》109(4)，787 - 795；诺恩斯，H.O.，德雷斯勒，G.R.等，1990年。Pax2在小鼠神经发生过程中的时空限制表达。《发育》109(4)，797 - 809；埃克尔斯，M.R.，沃利斯，L.J.等，1992年。PAX2基因在人胎儿肾脏和威尔姆斯瘤中的表达。《细胞生长与分化》3(5)，279 - 289]。在视觉系统中，功能丧失会导致脉络膜裂闭合缺失（称为缺损）、视神经星形胶质细胞缺失以及视交叉处轴突异常寻路[法弗，J.，桑杜拉切，R.等，1996年。小鼠Pax2(1Neu)突变与肾 - 缺损综合征家族中的人类PAX2突变相同，并导致脑、耳、眼和肾的发育缺陷。《美国国家科学院院刊》93(24)，13870 - 13875；托雷斯，M.，戈麦斯 - 帕尔多，E.等，1996年。Pax2有助于内耳模式形成和视神经轨迹。《发育》122(11)，3381 - 3391]。本研究旨在确定在正常发育时期之后，在鸡胚腹侧视杯中异位表达Pax2的影响，此时Pax2已不存在。在鸡胚腹侧视杯中进行Pax2的卵内电穿孔会导致缺损的形成，这是一种通常与Pax2表达缺失相关的情况。虽然Pax2的过表达似乎模拟了Pax2的缺失，但脉络膜裂闭合失败的机制与细胞命运从腹侧视网膜和视网膜色素上皮（RPE）转变为星形胶质细胞命运有关。此外，Pax2在RPE中的异位表达似乎对相邻的RPE具有非细胞自主效应，从而在RPE的位置形成异位神经视网膜。
