title: Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium.
abstract: BACKGROUND
  The main olfactory epithelium (MOE) in mammals is a specialized organ to detect odorous molecules in the external environment. The MOE consists of four types of cells: olfactory sensory neurons, supporting cells, basal cells, and microvillous cells. Among these, development and function of microvillous cells remain largely unknown. Recent studies have shown that a population of microvillous cells expresses the monovalent cation channel Trpm5 (transient receptor potential channel M5). To examine functional differentiation of Trpm5-expressing microvillous cells in the MOE, we investigated the expression and function of Skn-1a, a POU (Pit-Oct-Unc) transcription factor required for functional differentiation of Trpm5-expressing sweet, umami, and bitter taste bud cells in oropharyngeal epithelium and solitary chemosensory cells in nasal respiratory epithelium.
  
  
  RESULTS
  Skn-1a is expressed in a subset of basal cells and apical non-neuronal cells in the MOE of embryonic and adult mice. Two-color in situ hybridization revealed that a small population of Skn-1a-expressing cells was co-labeled with Mash1/Ascl1 and that most Skn-1a-expressing cells coexpress Trpm5. To investigate whether Skn-1a has an irreplaceable role in the MOE, we analyzed Skn-1a-deficient mice. In the absence of Skn-1a, olfactory sensory neurons differentiate normally except for a limited defect in terminal differentiation in ectoturbinate 2 of some of MOEs examined. In contrast, the impact of Skn-1a deficiency on Trpm5-expressing microvillous cells is much more striking: Trpm5, villin, and choline acetyltransferase, cell markers previously shown to identify Trpm5-expressing microvillous cells, were no longer detectable in Skn-1a-deficient mice. In addition, quantitative analysis demonstrated that the density of superficial microvillous cells was significantly decreased in Skn-1a-deficient mice.
  
  
  CONCLUSIONS
  Skn-1a is expressed in a minority of Mash1-positive olfactory progenitor cells and a majority of Trpm5-expressing microvillous cells in the main olfactory epithelium. Loss-of-function mutation of Skn-1a resulted in complete loss of Trpm5-expressing microvillous cells, whereas most of olfactory sensory neurons differentiated normally. Thus, Skn-1a is a critical regulator for the generation of Trpm5-expressing microvillous cells in the main olfactory epithelium in mice.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Junpei
authors.initials: J
authors.lastname: Yamashita
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohmoto
authors.forename: Imad
authors.initials: I
authors.lastname: Aoudé
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Ogura
authors.forename: Wangmei
authors.initials: W
authors.lastname: Luo
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Bachmanov
authors.forename: Weihong
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Bioengineering, Graduate School of Bioscience and Bioengineering, Tokyo Institute of Technology, Yokohama 226-8501, Japan. imatsumoto@monell.org.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Junji
authors.initials: J
authors.lastname: Hirota
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D050810:Octamer Transcription Factors / Q000378:metabolism*; D009830:Olfactory Bulb / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D050053:TRPM Cation Channels / Q000378:metabolism*
chemical_list: D050810:Octamer Transcription Factors; C084342:Pou2f3 protein, mouse; D050053:TRPM Cation Channels; C498617:Trpm5 protein, mouse