Activation of Wnt signaling reduces ipsilaterally projecting retinal ganglion cells in pigmented retina
Activation of Wnt signaling reduces ipsilaterally projecting retinal ganglion cells in pigmented retina
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DOI：
10.1242/dev.163212
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发表时间：
2018-11-01
期刊：
影响因子：
4.6
通讯作者：
Mason, Carol
中科院分区：
文献类型：
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作者：
Iwai-Takekoshi, Lena;Balasubramanian, Revathi;Mason, Carol
在哺乳动物白化病中，视网膜色素上皮（RPE）中的黑素生成被破坏与投射到同侧大脑的视网膜神经节细胞（RGC）较少相关，导致视网膜和视觉通路中的许多异常，特别是双眼视觉。为了进一步了解白化病患者RPE受损和同侧RGC投射减少之间的分子联系，我们比较了胚胎白化病和有色小鼠RPE中的基因表达。我们发现，Wnt通路，指导周边视网膜分化，一般来说，细胞增殖，是失调的白化病RPE。与色素性RPE相比，Wnt 2 b在白化病RPE中的表达扩大，并且扩大的区域邻接同侧RGC神经发生和沉降的位点。通过体内锂（Li+）处理在有色小鼠中Wnt信号传导的药理学活化将通常注定投射到同侧的Zic 2阳性RGC的数目减少到在白化病视网膜中观察到的数目。这些结果暗示了从RPE到神经视网膜的Wnt信号传导作为调节同侧RGC产生的潜在因素，从而调节白化病表型。
In mammalian albinism, disrupted melanogenesis in the retinal pigment epithelium (RPE) is associated with fewer retinal ganglion cells (RGCs) projecting ipsilaterally to the brain, resulting in numerous abnormalities in the retina and visual pathway, especially binocular vision. To further understand the molecular link between disrupted RPE and a reduced ipsilateral RGC projection in albinism, we compared gene expression in the embryonic albino and pigmented mouse RPE. We found that the Wnt pathway, which directs peripheral retinal differentiation and, generally, cell proliferation, is dysregulated in the albino RPE. Wnt2b expression is expanded in the albino RPE compared with the pigmented RPE, and the expanded region adjoins the site of ipsilateral RGC neurogenesis and settling. Pharmacological activation of Wnt signaling in pigmented mice by lithium (Li+) treatment in vivo reduces the number of Zic2-positive RGCs, which are normally fated to project ipsilaterally, to numbers observed in the albino retina. These results implicate Wnt signaling from the RPE to neural retina as a potential factor in the regulation of ipsilateral RGC production, and thus the albino phenotype.