Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland.
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland; University of Basel, 4058 Basel, Switzerland.
Neuron. 2014 Aug 6;83(3):586-600. doi: 10.1016/j.neuron.2014.06.020. Epub 2014 Jul 4.
The outer segments of cones serve as light detectors for daylight color vision, and their dysfunction leads to human blindness conditions. We show that the cone-specific disruption of DGCR8 in adult mice led to the loss of miRNAs and the loss of outer segments, resulting in photoreceptors with significantly reduced light responses. However, the number of cones remained unchanged. The loss of the outer segments occurred gradually over 1 month, and during this time the genetic signature of cones decreased. Reexpression of the sensory-cell-specific miR-182 and miR-183 prevented outer segment loss. These miRNAs were also necessary and sufficient for the formation of inner segments, connecting cilia and short outer segments, as well as light responses in stem-cell-derived retinal cultures. Our results show that miR-182- and miR-183-regulated pathways are necessary for cone outer segment maintenance in vivo and functional outer segment formation in vitro.
锥体的外节充当日光色觉的光探测器，其功能障碍导致人类失明。我们表明，成年小鼠中 DGCR8 的锥体特异性破坏导致 miRNA 的丢失和外节的丢失，从而导致光感受器的光反应显著降低。然而，锥体的数量保持不变。外节逐渐丢失，历时 1 个月，在此期间，锥体的遗传特征逐渐减少。感觉细胞特异性 miR-182 和 miR-183 的重新表达可防止外节丢失。这些 miRNA 对于内节、连接纤毛和短外节的形成以及干细胞衍生的视网膜培养物中的光反应也是必需和充分的。我们的结果表明，miR-182 和 miR-183 调节的途径对于体内锥体外节的维持和体外功能性外节的形成是必需的。
