title: Different requirements for GFRα2-signaling in three populations of cutaneous sensory neurons.
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.
authors.affiliation: Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: Jussi
authors.initials: J
authors.lastname: Kupari
authors.affiliation: Institute of Biomedicine, Anatomy, University of Helsinki, Helsinki, Finland.
authors.forename: Matti S
authors.initials: MS
authors.lastname: Airaksinen
mesh_terms: D000818:Animals; D048429:Cell Size; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D055786:Gene Knockout Techniques; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018859:Hair Follicle / Q000294:innervation; D008297:Male; D051379:Mice; D016900:Neurofilament Proteins / Q000378:metabolism; D051096:Proto-Oncogene Proteins c-ret / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; C528431:Mrge protein, mouse; D016900:Neurofilament Proteins; D043562:Receptors, G-Protein-Coupled; C051774:neurofilament protein H; D014446:Tyrosine 3-Monooxygenase; D051096:Proto-Oncogene Proteins c-ret; C494999:Ret protein, mouse
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