TrkC kinase expression in distinct subsets of cutaneous trigeminal innervation and nonneuronal cells

Abstract

Neurotrophin-activated receptor tyrosine kinases (Trks) regulate sensory neuron survival, differentiation, and function. To permanently mark cells that ever express TrkC-kinase, mice with lacZ and GFP reporters of Cre recombinase activity were crossed with mice having IRES-cre inserted into the kinase-containing exon of the TrkC gene. Prenatal reporter expression matched published locations of TrkC-expression. Postnatally, more trigeminal neurons and types of mystacial pad innervation expressed reporter than immunodetectable TrkC, indicating that some innervation transiently expresses TrkC-kinase. Reporter-tagged neurons include all those that immunolabel for TrkC, a majority for TrkB, and a small proportion for TrkA. TrkA neurons expressing TrkC-reporter range from small to large size and supply well-defined types of mystacial pad innervation. Virtually all small neurons and C-fiber innervation requires TrkA to develop, but TrkC-reporter is present in only a small proportion that uniquely innervates piloneural complexes of guard hairs and inner conical bodies of vibrissa follicle-sinus complexes. TrkC-reporter is expressed in nearly all presumptive Adelta innervation, which is all eliminated in TrkA knockouts and partially eliminated in TrkC knockouts. Many types of Abeta-fiber innervation express TrkC-reporter including all Merkel, spiny, and circumferentially oriented lanceolate endings, and some reticular and longitudinally oriented lanceolate endings. Only Merkel endings require TrkC to develop and survive, whereas the other endings require TrkA and/or TrkB. Thus, TrkC is required for the existence of some types of innervation that express TrkC, but may have different functions in others. Many types of nonneuronal cells affiliated with hair follicles and blood vessels also express TrkC-reporter but lack immunodetectable TrkC.