Taiwan International Graduate Program in Interdisciplinary Neuroscience, National Yang-Ming University and Academia Sinica, Taipei, Taiwan.
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
Elife. 2021 Mar 31;10:e63768. doi: 10.7554/eLife.63768.
Although the function of microRNAs (miRNAs) during embryonic development has been intensively studied in recent years, their postnatal physiological functions remain largely unexplored due to inherent difficulties with the presence of redundant paralogs of the same seed. Thus, it is particularly challenging to uncover miRNA functions at neural circuit level since animal behaviors would need to be assessed upon complete loss of miRNA family functions. Here, we focused on the neural functions of MiR34/449 that manifests a dynamic expression pattern in the spinal cord from embryonic to postnatal stages. Our behavioral assays reveal that the loss of MiR34/449 miRNAs perturb thermally induced pain response thresholds and compromised delicate motor output in mice. Mechanistically, MiR34/449 directly target and to fine-tune the precise number of a sub-population of motor synergy encoder (MSE) neurons. Thus, MiR34/449 fine-tunes optimal development of Satb1/2 interneurons in the spinal cord, thereby refining explicit sensory-to-motor circuit outputs.
尽管近年来人们对 microRNAs（miRNAs）在胚胎发育过程中的功能进行了深入研究，但由于同一种子的冗余同源物的存在，其出生后的生理功能在很大程度上仍未得到探索。因此，在神经回路水平上揭示 miRNA 的功能特别具有挑战性，因为需要在 miRNA 家族功能完全缺失的情况下评估动物行为。在这里，我们专注于 MiR34/449 的神经功能，它在脊髓中表现出从胚胎到出生后的动态表达模式。我们的行为分析表明，MiR34/449 缺失会干扰热诱导的疼痛反应阈值，并损害小鼠精细的运动输出。从机制上讲，MiR34/449 可以直接靶向和来微调运动协同编码器（MSE）神经元亚群的精确数量。因此，MiR34/449 可以微调脊髓中 Satb1/2 中间神经元的最佳发育，从而改善明确的感觉-运动回路输出。
