Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.
Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.
复制标题
DOI：
10.1016/j.ydbio.2017.07.012
复制
发表时间：
2017-10-01
影响因子：
2.7
通讯作者：
Eggenschwiler JT
中科院分区：
文献类型：
--
作者：
Burnett JB;Lupu FI;Eggenschwiler JT
将脊椎动物的眼睛图案化为视柄、视网膜色素上皮（RPE）和神经视网膜（NR）区域依赖于许多信号传导途径，但是这些信号如何被视祖细胞解释还不清楚。初级纤毛是一种基于微管的细胞器，对Hedgehog（Hh）信号传导至关重要，但它也参与了其他信号传导途径的调节。在这里，我们表明，视原基纤毛在早期眼睛的发展和纤毛是必不可少的适当的图案和小鼠眼睛的形态发生。Ift172突变体不能产生初级纤毛，并表现出类似于Gli3突变体的图案缺陷，这表明在眼睛形成过程中需要纤毛来限制Hh活性。Ift122突变体产生的纤毛形态异常，产生的视泡不能内陷形成视杯。这些突变体也缺乏透镜、RPE和NR的形成。这种表型特征伴随着强烈的异位Hh途径活性，这由改变的基因表达模式证明。从Ift 122突变体中去除GLI 2挽救了视杯和透镜形态发生以及RPE和NR特化的几个方面。总的来说，我们的数据表明，初级纤毛的正确组装是关键的限制刺猬途径在眼睛形成的小鼠。
Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The primary cilium is a microtubule-based organelle that is essential for Hedgehog (Hh) signaling, but it has also been implicated in the regulation of other signaling pathways. Here, we show that the optic primordium is ciliated during early eye development and that ciliogenesis is essential for proper patterning and morphogenesis of the mouse eye. Ift172 mutants fail to generate primary cilia and exhibit patterning defects that resemble those of Gli3 mutants, suggesting that cilia are required to restrict Hh activity during eye formation. Ift122 mutants, which produce cilia with abnormal morphology, generate optic vesicles that fail to invaginate to produce the optic cup. These mutants also lack formation of the lens, RPE and NR. Such phenotypic features are accompanied by strong, ectopic Hh pathway activity, evidenced by altered gene expression patterns. Removal of GLI2 from Ift122 mutants rescued several aspects of optic cup and lens morphogenesis as well as RPE and NR specification. Collectively, our data suggest that proper assembly of primary cilia is critical for restricting the Hedgehog pathway during eye formation in the mouse.
登录
查看更多内容
影响因子：
9.2
作者：
EKKER, SC;UNGAR, AR;BEACHY, PA
通讯作者：
BEACHY, PA
影响因子：
--
作者：
Lauter G;Söll I;Hauptmann G
通讯作者：
Hauptmann G
影响因子：
30.8
作者：
HUI, CC;JOYNER, AL
通讯作者：
JOYNER, AL
影响因子：
4.5
作者：
Chang CF;Chang YT;Millington G;Brugmann SA
通讯作者：
Brugmann SA
初级纤毛通过 Lkb1 调节 mTORC1 活性和细胞大小。
影响因子：
21.3
作者：
Boehlke, Christopher;Kotsis, Fruzsina;Patel, Vishal;Braeg, Simone;Voelker, Henriette;Bredt, Saskia;Beyer, Theresa;Janusch, Heike;Hamann, Christoph;Goedel, Markus;Mueller, Klaus;Herbst, Martin;Hornung, Miriam;Doerken, Mara;Koettgen, Michael;Nitschke, Roland;Igarashi, Peter;Walz, Gerd;Kuehn, E. Wolfgang
通讯作者：
Kuehn, E. Wolfgang