Nociceptor subtypes are born continuously over DRG development.

Nociceptor subtypes are born continuously over DRG development.
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DOI:
10.1016/j.ydbio.2021.07.018
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发表时间:
2021-11
影响因子:
2.7
通讯作者:
Lai HC
Lai HC
中科院分区:
生物学3区
文献类型:
--
作者:
Landy MA;Goyal M;Lai HC

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背根神经节(DRG)中的感觉神经发生以两波分化发生,其中较大的有髓鞘本体感受和低阈值机械感受(LTMR)神经元在较小的无髓鞘(C)伤害感受神经元之前分化。这种时间差异是根据DRG索马细胞大小的早期出生日期研究建立的。然而,感觉神经元,特别是伤害感受器的分子亚型之间的出生日期的区别是未知的。在这里,我们使用胸苷类似物EdU来标记退出有丝分裂的发育中的神经元,结合已知的感觉神经元标记物的共标记来评估小鼠腰DRG神经元的出生日期。我们发现不同的伤害感受器亚型出生在相似的时间尺度上,在E9.5到E13.5之间连续出生,在E10.5到E11.5之间达到高峰。值得注意的是,我们发现,薄髓鞘Aδ纤维伤害感受器和肽能C纤维出生在E10.5和E11.5之间比以前认为的更广泛,而非肽能C纤维和C-LTMR出生的高峰期为E11.5。此外,我们发现在特定时间点出生的伤害感受器亚型的百分比对于任何给定的伤害感受器细胞类型标记物是相同的,这表明对细胞类型多样性的内在或外在影响在整个发育时间内类似地发生。总体而言,出生模式仍然符合经典的“两波”描述,因为触觉和本体感受纤维主要在E10.5出生,但表明伤害感受器具有稍宽的出生日期波,不同的伤害感受器亚型在整个感觉神经发生中不断分化,而不管髓鞘形成。
Sensory neurogenesis in the dorsal root ganglion (DRG) occurs in two waves of differentiation with larger, myelinated proprioceptive and low-threshold mechanoreceptor (LTMR) neurons differentiating before smaller, unmyelinated (C) nociceptive neurons. This temporal difference was established from early birthdating studies based on DRG soma cell size. However, distinctions in birthdates between molecular subtypes of sensory neurons, particularly nociceptors, is unknown. Here, we assess the birthdate of lumbar DRG neurons in mice using a thymidine analog, EdU, to label developing neurons exiting mitosis combined with co-labeling of known sensory neuron markers. We find that different nociceptor subtypes are born on similar timescales, with continuous births between E9.5 to E13.5, and peak births from E10.5 to E11.5. Notably, we find that thinly myelinated Aδ-fiber nociceptors and peptidergic C-fibers are born more broadly between E10.5 and E11.5 than previously thought and that non-peptidergic C-fibers and C-LTMRs are born with a peak birth date of E11.5. Moreover, we find that the percentages of nociceptor subtypes born at a particular timepoint are the same for any given nociceptor cell type marker, indicating that intrinsic or extrinsic influences on cell type diversity are occurring similarly across developmental time. Overall, the patterns of birth still fit within the classical “two wave” description, as touch and proprioceptive fibers are born primarily at E10.5, but suggest that nociceptors have a slightly broader wave of birthdates with different nociceptor subtypes continually differentiating throughout sensory neurogenesis irrespective of myelination.
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