Kupari Jussi, Airaksinen Matti S
Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
PLoS One. 2014 Aug 11;9(8):e104764. doi: 10.1371/journal.pone.0104764. eCollection 2014.
Many primary sensory neurons in mouse dorsal root ganglia (DRG) express one or several GFRα's, the ligand-binding receptors of the GDNF family, and their common signaling receptor Ret. GFRα2, the principal receptor for neurturin, is expressed in most of the small nonpeptidergic DRG neurons, but also in some large DRG neurons that start to express Ret earlier. Previously, GFRα2 has been shown to be crucial for the soma size of small nonpeptidergic nociceptors and for their target innervation of glabrous epidermis. However, little is known about this receptor in other Ret-expressing DRG neuron populations. Here we have investigated two populations of Ret-positive low-threshold mechanoreceptors that innervate different types of hair follicles on mouse back skin: the small C-LTMRs and the large Aβ-LTMRs. Using GFRα2-KO mice and immunohistochemistry we found that, similar to the nonpeptidergic nociceptors, GFRα2 controls the cell size but not the survival of both C-LTMRs and Aβ-LTMRs. In contrast to the nonpeptidergic neurons, GFRα2 is not required for the target innervation of C-LTMRs and Aβ-LTMRs in the back skin. These results suggest that different factors drive target innervation in these three populations of neurons. In addition, the observation that the large Ret-positive DRG neurons lack GFRα2 immunoreactivity in mature animals suggests that these neurons switch their GFRα signaling pathways during postnatal development.
小鼠背根神经节(DRG)中的许多初级感觉神经元表达一种或几种GFRα,即胶质细胞源性神经营养因子(GDNF)家族的配体结合受体,以及它们的共同信号受体Ret。GFRα2是神经营养因子的主要受体,在大多数小的非肽能DRG神经元中表达,但也在一些较早开始表达Ret的大的DRG神经元中表达。此前已表明,GFRα2对于小的非肽能伤害感受器的胞体大小及其对无毛表皮的靶神经支配至关重要。然而,对于其他表达Ret的DRG神经元群体中的这种受体,我们了解甚少。在这里,我们研究了支配小鼠背部皮肤不同类型毛囊的两类Ret阳性低阈值机械感受器:小的C类低阈值机械感受器(C-LTMRs)和大的Aβ类低阈值机械感受器(Aβ-LTMRs)。使用GFRα2基因敲除小鼠和免疫组织化学方法,我们发现,与非肽能伤害感受器类似,GFRα2控制C-LTMRs和Aβ-LTMRs的细胞大小,但不影响它们的存活。与非肽能神经元不同,背部皮肤中C-LTMRs和Aβ-LTMRs的靶神经支配不需要GFRα2。这些结果表明,不同的因素驱动这三类神经元的靶神经支配。此外,在成熟动物中,大的Ret阳性DRG神经元缺乏GFRα2免疫反应性这一观察结果表明,这些神经元在出生后发育过程中会切换其GFRα信号通路。
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