title: Dependence on the transcription factor Shox2 for specification of sensory neurons conveying discriminative touch.
abstract: Touch sensation is mediated by specific subtypes of sensory neurons which develop in a hierarchical process from common early progenitor neurons, but the molecular mechanism that underlies diversification of touch-sensitive mechanoreceptive neurons is not fully known. Here, we use genetically manipulated mice to examine whether the transcription factor short stature homeobox 2 (Shox2) participates in the acquisition of neuronal subtypes conveying touch sensation. We show that Shox2 encodes the development of category I low-threshold mechanoreceptive neurons in glabrous skin, i.e. discriminative touch-sensitive neurons which form innervations of epidermal Merkel cell and Meissner corpuscles. In contrast, other sensory fiber endings, including those innervating Pacinian corpuscles, are not dependent on Shox2. Shox2 is expressed in neurons of most or all classes of sensory neurons at early embryonic stages and is later confined to touch-sensitive neurons expressing Ret and/or TrkB. Conditional deletion of Shox2 and analysis of Runx3(-/-);Bax(-/-) mutant mice reveals that Runx3 is suppressing Shox2 while Shox2 is necessary for TrkB expression, and that these interactions are necessary for diversification of TrkB(+) and TrkC(+) mechanoreceptive neurons. In particular, development of TrkB(+)/Ret(+) and TrkB(+)/Ret(-) touch-sensitive neurons is critically dependent on Shox2. Consistently, Shox2 conditional mutant mice demonstrate a dramatic impairment of light touch responses. These results show that Shox2 is required for specification of a subclass of TrkB(+) sensory neurons which convey the sensation of discriminative touch arising from stimuli of the skin.
authors: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
authors: Hind
authors: H
authors: Abdo
authors: Lili
authors: L
authors: Li
authors: Francois
authors: F
authors: Lallemend
authors: Isabelle
authors: I
authors: Bachy
authors: Xiao-Jun
authors: XJ
authors: Xu
authors: Frank L
authors: FL
authors: Rice
authors: Patrik
authors: P
authors: Ernfors
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008465:Mechanoreceptors / Q000166:cytology / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D018862:Merkel Cells / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000166:cytology / Q000502:physiology; D010141:Pacinian Corpuscles / Q000166:cytology / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D020812:Receptor, trkC / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000502:physiology*; D014110:Touch / Q000502:physiology*; D055698:Touch Perception / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D018398:Homeodomain Proteins; C493730:Runx3 protein, mouse; C484663:Shox2 protein, mouse; D051028:bcl-2-Associated X Protein; D051096:Proto-Oncogene Proteins c-ret; D020813:Receptor, trkB; D020812:Receptor, trkC; C494999:Ret protein, mouse