Abstract
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.
Highlights
The primary somatosensory neurons responsible for conducting different modalities of information from the external world are located outside the CNS in the dorsal root ganglia (DRG) and trigeminal ganglia
We analyzed the size distribution of these cells and found that the MrgD+ neurons were drastically smaller in KO mice than in wild type (WT) animals (Fig. 1E, F, G)
The key finding of the present study is that GFRa2 is required for proper size of both tyrosine hydroxylase (TH)+/C-LTMR and rapidly adapting (RA) Ab-LTMR neurons, but is expendable for their target innervation of hair follicles, in contrast to the MrgD+ neurons that depend on GFRa2 for both cell size and target innervation of the epidermis
Summary
The primary somatosensory neurons responsible for conducting different modalities of information from the external world are located outside the CNS in the (spinal) dorsal root ganglia (DRG) and (cranial) trigeminal ganglia. Most DRG neurons express the receptor tyrosine kinase Ret, the main signaling receptor for the GDNF family of neurotrophic factors [1]. This family consists of four ligands: GDNF, neurturin (NRTN), artemin, and persephin [2]. They signal through Ret via cognate GFRa receptors, three of which (GFRa1 through GFRa3) are expressed in partially overlapping sensory neuron populations [2]. These ‘‘early-Ret’’ neurons have been shown to constitute a group of myelinated, rapidly adapting (RA) low threshold mechanoreceptors (AbLTMRs) [15,16,17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
