Department of Neuroscience, Psychology, Drug Research and Child Health NEUROFARBA University of Florence, Area San Salvi-Pad. 26, 50135 Florence, Italy.
Institute of Neuroscience, National Research Council, Via Moruzzi, 1 56124 Pisa, Italy.
Nat Commun. 2017 May 23;8:15488. doi: 10.1038/ncomms15488.
MicroRNAs (miRNAs) are known to mediate post-transcriptional gene regulation, but their role in postnatal brain development is still poorly explored. We show that the expression of many miRNAs is dramatically regulated during functional maturation of the mouse visual cortex with miR-132/212 family being one of the top upregulated miRNAs. Age-downregulated transcripts are significantly enriched in miR-132/miR-212 putative targets and in genes upregulated in miR-132/212 null mice. At a functional level, miR-132/212 deletion affects development of receptive fields of cortical neurons determining a specific impairment of binocular matching of orientation preference, but leaving orientation and direction selectivity unaltered. This deficit is associated with reduced depth perception in the visual cliff test. Deletion of miR-132/212 from forebrain excitatory neurons replicates the binocular matching deficits. Thus, miR-132/212 family shapes the age-dependent transcriptome of the visual cortex during a specific developmental window resulting in maturation of binocular cortical cells and depth perception.
微小 RNA(miRNAs)被认为可以介导转录后基因调控,但它们在出生后大脑发育中的作用仍未得到充分探索。我们发现,许多 miRNAs 的表达在小鼠视觉皮层的功能成熟过程中受到显著调控,miR-132/212 家族是上调最明显的 miRNAs 之一。年龄下调的转录物在 miR-132/miR-212 潜在靶标和 miR-132/212 缺失小鼠中上调的基因中显著富集。在功能水平上,miR-132/212 的缺失会影响皮层神经元感受野的发育,导致双眼对方向偏好的匹配出现特定障碍,但不改变方向和方向选择性。这种缺陷与视觉悬崖测试中深度知觉的降低有关。从前脑兴奋性神经元中删除 miR-132/212 可重现双眼匹配障碍。因此,miR-132/212 家族在特定的发育窗口期间塑造视觉皮层的年龄依赖性转录组,从而导致双眼皮层细胞的成熟和深度知觉。