title: Emergence of functional sensory subtypes as defined by transient receptor potential channel expression.
abstract: The existence of heterogeneous populations of dorsal root ganglion (DRG) neurons conveying different somatosensory information is the basis for the perception of touch, temperature, and pain. A differential expression of transient receptor potential (TRP) cation channels contributes to this functional heterogeneity. However, little is known about the development of functionally diverse neuronal subpopulations. Here, we use calcium imaging of acutely dissociated mouse sensory neurons and quantitative reverse transcription PCR to show that TRP cation channels emerge in waves, with the diversification of functional groups starting at embryonic day 12.5 (E12.5) and extending well into the postnatal life. Functional responses of voltage-gated calcium channels were present in DRG neurons at E11.5 and reached adult levels by E14.5. Responses to capsaicin, menthol, and cinnamaldehyde were first seen at E12.5, E16.5, and postnatal day 0 (P0), when the mRNA for TRP cation channel, subfamily V, member 1 (TRPV1), TRP cation channel, subfamily M, member 8 (TRPM8), and TRP cation channel, subfamily A, member 1 (TRPA1), respectively, was first detected. Cold-sensitive neurons were present before the expression or functional responses of TRPM8 or TRPA1. Our data support a lineage relationship in which TRPM8- and TRPA1-expressing sensory neurons derive from the population of TRPV1-expressing neurons. The TRPA1 subpopulation of neurons emerges independently in two distinct classes of nociceptors: around birth in the peptidergic population and after P14 in the nonpeptidergic class. This indicates that neurons with similar receptive properties can be generated in different sublineages at different developmental stages. This study describes for the first time the emergence of functional subtypes of sensory neurons, providing new insight into the development of nociception and thermoreception.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Hjerling-Leffler
authors.forename: Mona
authors.initials: M
authors.lastname: Alqatari
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D003080:Cold Temperature; D004622:Embryo, Mammalian; D047108:Embryonic Development; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008610:Menthol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009475:Neurons, Afferent / Q000145:classification* / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D037121:Plant Lectins / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics; D013823:Thermoreceptors / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D012333:RNA, Messenger; D000074025:TRPA1 Cation Channel; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D008610:Menthol; D000171:Acrolein; D002211:Capsaicin; C012843:cinnamaldehyde