Somatotopic organization of central arbors from nociceptive afferents develops independently of their intact peripheral target innervation.
Somatotopic organization of central arbors from nociceptive afferents develops independently of their intact peripheral target innervation.
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DOI：
10.1002/cne.24533
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发表时间：
2018-12-15
期刊：
影响因子：
--
通讯作者：
Luo W
中科院分区：
文献类型：
--
作者：
Olson W;Luo W
感觉地图的重要功能区域在感觉通路和皮层中过度表达，但其潜在的发育机制尚不清楚。在脊髓背角（DH），我们最近表明，爪支配Mrgprd+非肽能伤害性感受器显示独特的中央乔木形态，以及与增加突触传递效率和提高敏感性的远端肢体皮肤。鉴于Mrgprd+神经元的外周和中央乔木形成在出生时共同发生，我们测试了来自不同皮肤区域和/或出生后重组机制的外周线索是否可以指示中央乔木之间的这种躯体位置差异。我们发现，虽然终端生长/细化发生在出生后早期的发展过程中，在皮肤和DH，出生后细化中央终端之前，周边终端。此外，我们使用Ret的单细胞消融来从遗传上破坏Mrgprd+神经元的表皮神经支配，并发现它们的中央乔木之间的躯体位置差异不受这种操作的影响。最后，我们看到，区域特定的Mrgprd+中央终端乔木是目前从出生后的最早阶段，皮肤终端是明显的。总之，我们发现Mrgprd+神经元中枢乔木的区域特异性组织在最初的中央终末形成后不久就存在，其可能独立于外周靶神经支配而发展。我们的数据表明，无论是细胞内在的和/或DH预图案化的机制可能建立这种躯体部位的差异。 哺乳动物伤害感受器的主要类别的躯体位置组织在出生后的早期阶段是明显的。我们在P3小鼠脊髓中对Mrgprd+伤害感受器轴突主干进行了稀疏遗传追踪。脊髓神经支配早期阶段存在区域特异性形态，这表明预模式机制可以建立这些差异。
Functionally important regions of sensory maps are overrepresented in the sensory pathways and cortex, but the underlying developmental mechanisms are not clear. In the spinal cord dorsal horn (DH), we recently showed that paw innervating Mrgprd+ non-peptidergic nociceptors display distinctive central arbor morphologies that well correlate with increased synapse transmission efficiency and heightened sensitivity of distal limb skin. Given that peripheral and central arbor formation of Mrgprd+ neurons co-occurs around the time of birth, we tested whether peripheral cues from different skin areas and/or postnatal reorganization mechanisms could instruct this somatotopic difference among central arbors. We found that, while terminal outgrowth/refinement occurs during early postnatal development in both the skin and the DH, postnatal refinement of central terminals precedes that of peripheral terminals. Further, we used single-cell ablation of Ret to genetically disrupt epidermal innervation of Mrgprd+ neurons and revealed that the somatotopic difference among their central arbors was unaffected by this manipulation. Finally, we saw that region-specific Mrgprd+ central terminal arbors are present from the earliest postnatal stages, before skin terminals are evident. In ummary, we find that region-specific organization of Mrgprd+ neuron central arbors is present shortly after initial central terminal formation, which likely develops independently of peripheral target innervation. Our data suggest that either cell-intrinsic and/or DH pre-patterning mechanisms are likely to establish this somatotopic difference. Somatotopic organization of a major class of mammalian nociceptors is evident at early postnatal stages. We performed sparse genetic tracing of Mrgprd+ nociceptor axonal arbors in P3 mouse spinal cords. The presence of region-specific morphologies at early stages of spinal cord innervation suggests that pre-patterning mechanisms could establish these differences.
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