Fgf8 Expression and Degradation of Retinoic Acid Are Required for Patterning a High-Acuity Area in the Retina.

Fgf8 Expression and Degradation of Retinoic Acid Are Required for Patterning a High-Acuity Area in the Retina.
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DOI:
10.1016/j.devcel.2017.05.024
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发表时间:
2017-07-10
期刊:
影响因子:
11.8
通讯作者:
Cepko CL
Cepko CL
中科院分区:
生物学1区
文献类型:
--
作者:
da Silva S;Cepko CL

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高度依赖于其视觉系统的物种具有专门的视网膜区域,以实现高敏锐度视觉,例如,人类的中央凹虽然对我们的日常活动至关重要,但对驱动视网膜高敏度区域(哈斯)发育的机制知之甚少。以鸡为模型,我们发现成纤维细胞生长因子8(Fgf 8)在HAA原基中精确且动态的表达模式,该表达模式受到降解维甲酸(RA)的酶的调节。RA信号的瞬时操纵,或Fgf8表达的减少,破坏了HAA图案化的几个特征,包括光感受器分布,神经节细胞密度和中间神经元的组织。值得注意的是,在人类中也发现了RA信号传导成分的模式化表达,这表明RA也在建立人类中央凹中发挥作用。负责高视力的视网膜区域(中央凹)发育的分子机制在很大程度上是未知的。Da Silva和Cepko揭示了视黄酸(RA)信号的局部抑制通过Fgf8调节鸡高敏区域的形成。RA也可能控制人类视网膜中央凹的发育。
Species that are highly reliant on their visual system have a specialized retinal area subserving high-acuity vision, e.g., the fovea in humans. Although of critical importance for our daily activities, little is known about the mechanisms driving the development of retinal high-acuity areas (HAAs). Using the chick as a model, we found a precise and dynamic expression pattern of fibroblast growth factor 8 (Fgf8) in the HAA anlage, which was regulated by enzymes that degrade retinoic acid (RA). Transient manipulation of RA signaling, or reduction of Fgf8 expression, disrupted several features of HAA patterning, including photoreceptor distribution, ganglion cell density, and organization of interneurons. Notably, patterned expression of RA signaling components was also found in humans, suggesting that RA also plays a role in setting up the human fovea. Molecular mechanisms underlying the development of the region of the retina responsible for high-acuity vision (the fovea) are largely unknown. Da Silva and Cepko reveal that localized suppression of retinoic acid (RA) signaling regulates chick high-acuity area formation through Fgf8. RA may also control human fovea development.
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