Dual Innervation of Neonatal Merkel Cells in Mouse Touch Domes
Dual Innervation of Neonatal Merkel Cells in Mouse Touch Domes
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DOI：
10.1371/journal.pone.0092027
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发表时间：
2014-03-17
期刊：
影响因子：
3.7
通讯作者：
Luo, Wenqin
中科院分区：
文献类型：
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作者：
Niu, Jingwen;Vysochan, Anna;Luo, Wenqin
默克尔细胞-神经突复合体是介导辨别性触觉的专门的机械感觉终末器官。已经确定表达神经丝重链（NFH）的I型慢适应（SAI）机械感受器支配默克尔细胞。先前显示，神经营养因子NT 3及其受体TrkC在控制NFH+纤维的触丘默克尔细胞神经支配中起关键作用。此外，表达另一种神经营养性酪氨酸受体激酶（NTRK）Ret的神经纤维也支配触丘默克尔细胞。然而，对NT 3/TrkC信号传导有反应的传入神经与表达Ret的传入神经之间的关系尚不清楚。这些Ret（+）纤维是否属于早期或晚期Ret（+）DRG神经元也存在争议，这是基于TrkA的共表达和发育依赖性来定义的。为了解决这些问题，我们从遗传学上追踪了Ret（+）和TrkC（+）纤维，并分析了它们对TrkA的发育依赖性。我们发现，新生小鼠触丘中的默克尔细胞接受两种类型的纤维的神经支配：一组是Ret（+），而另一个子集表达TrkC和NFH。此外，Ret（+）纤维的存活和正常神经支配依赖于TrkA，而NFH+默克尔细胞神经支配纤维在TrkA突变小鼠中几乎不变，这支持Ret（+）和NFH+/TrkC（+）传入是两个不同的组。另一方面，Ret信号在新生儿触球的神经支配中起着次要的作用。相比之下，无毛皮肤中的默克尔细胞主要与NFH+/TrkC（+）传入接触。两者合计，我们的研究结果表明，新生默克尔细胞周围的毛囊接受双重神经支配，而默克尔细胞在光滑的皮肤主要是由SAI机械感受器支配。此外，我们的研究结果表明，新生儿Ret（+）默克尔细胞的支配纤维最有可能属于晚期而不是早期Ret（+）DRG神经元。
Merkel cell-neurite complexes are specialized mechanosensory end organs that mediate discriminative touch sensation. It is well established that type I slowly adapting (SAI) mechanoreceptors, which express neural filament heavy chain (NFH), innervate Merkel cells. It was previously shown that neurotrophic factor NT3 and its receptor TrkC play crucial roles in controlling touch dome Merkel cell innervation of NFH+ fibers. In addition, nerve fibers expressing another neurotrophic tyrosine receptor kinase (NTRK), Ret, innervate touch dome Merkel cells as well. However, the relationship between afferents responsive to NT3/TrkC signaling and those expressing Ret is unclear. It is also controversial if these Ret(+) fibers belong to the early or late Ret(+) DRG neurons, which are defined based on the co-expression and developmental dependence of TrkA. To address these questions, we genetically traced Ret(+) and TrkC(+) fibers and analyzed their developmental dependence on TrkA. We found that Merkel cells in neonatal mouse touch domes receive innervation of two types of fibers: one group is Ret(+), while the other subset expresses TrkC and NFH. In addition, Ret(+) fibers depend on TrkA for their survival and normal innervation whereas NFH+ Merkel cell innervating fibers are almost unaltered in TrkA mutant mice, supporting that Ret(+) and NFH+/TrkC(+) afferents are two distinct groups. Ret signaling, on the other hand, plays a minor role for the innervation of neonatal touch domes. In contrast, Merkel cells in the glabrous skin are mainly contacted by NFH+/TrkC(+) afferents. Taken together, our results suggest that neonatal Merkel cells around hair follicles receive dual innervation while Merkel cells in the glabrous skin are mainly innervated by only SAI mechanoreceptors. In addition, our results suggest that neonatal Ret(+) Merkel cell innervating fibers most likely belong to the late but not early Ret(+) DRG neurons.