title: Retinoic acid regulates olfactory progenitor cell fate and differentiation.
abstract: BACKGROUND
  In order to fulfill their chemosensory function, olfactory neurons are in direct contact with the external environment and are therefore exposed to environmental aggressive factors. Olfaction is maintained through life because, unlike for other sensory neuroepithelia, olfactory neurons have a unique capacity to regenerate after trauma. The mechanisms that control the ontogenesis and regenerative ability of these neurons are not fully understood. Here, we used various experimental approaches in two model systems (chick and mouse) to assess the contribution of retinoic acid signaling in the induction of the olfactory epithelium, the generation and maintenance of progenitor populations, and the ontogenesis and differentiation of olfactory neurons.
  
  
  RESULTS
  We show that retinoic acid signaling, although dispensable for initial induction of the olfactory placode, plays a key role in neurogenesis within this neuroepithelium. Retinoic acid depletion in the olfactory epithelium, both in chick and mouse models, results in a failure of progenitor cell maintenance and, consequently, differentiation of olfactory neurons is not sustained. Using an explant system, we further show that renewal of olfactory neurons is hindered if the olfactory epithelium is unable to synthesize retinoic acid.
  
  
  CONCLUSIONS
  Our data show that retinoic acid is not a simple placodal inductive signal, but rather controls olfactory neuronal production by regulating the fate of olfactory progenitor cells. Retinaldehyde dehydrogenase 3 (RALDH3) is the key enzyme required to generate retinoic acid within the olfactory epithelium.
authors.affiliation: Laboratory for Sensory Development, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan.
authors.forename: Marie
authors.initials: M
authors.lastname: Paschaki
authors.forename: Laura
authors.initials: L
authors.lastname: Cammas
authors.forename: Yuko
authors.initials: Y
authors.lastname: Muta
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Siu-Shan
authors.initials: SS
authors.lastname: Mak
authors.forename: Monika
authors.initials: M
authors.lastname: Rataj-Baniowska
authors.forename: Valérie
authors.initials: V
authors.lastname: Fraulob
authors.forename: Pascal
authors.initials: P
authors.lastname: Dollé
authors.forename: Raj K
authors.initials: RK
authors.lastname: Ladher
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D051379:Mice; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects*; D009831:Olfactory Mucosa / Q000166:cytology / Q000187:drug effects; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D014212:Tretinoin