title: Conditionally immortalized clonal cell lines from the mouse olfactory placode differentiate into olfactory receptor neurons.
abstract: To test extracellular signals that direct the development of the olfactory system, we have generated clonal temperature-sensitive cell lines that represent distinct cellular lineages derived from the E10 mouse olfactory placode. Two of these lines, OP6 and OP27, express (at the permissive temperature), a transcriptional profile representing intermediate-late developmental stages in the olfactory receptor neuron (ORN) lineage. At the nonpermissive temperature, both OP6 and OP27 cells can be induced by all-trans retinoic acid to differentiate into a population of mature bipolar ORN-like cells. In response to retinoic acid, differentiated OP6 and OP27 down-regulate neuron-specific transcription factors required for early stages of neuronal differentiation, and shift active components of the neurotrophin signaling cascade (Trk receptors) into a kinase inactive state. When morphologically mature, OP6 and OP27 express the mature ORN chemosensory signaling components, olfactory G-protein (G(olf)), Type III adenylate cyclase (ACIII), OCNC1, and the olfactory marker protein (OMP). OP27 expresses one odorant receptor, OR 27-3. OP6 expresses two very closely related receptors, OR 6-13 and OR 6-8. Voltage-gated sodium and potassium channels resembling those recorded from primary cultures of ORNs can also be recorded from a subset of differentiated OP6 cells.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4.
authors.forename: Nicola
authors.initials: N
authors.lastname: Illing
authors.forename: Sihaam
authors.initials: S
authors.lastname: Boolay
authors.forename: Jenny S
authors.initials: JS
authors.lastname: Siwoski
authors.forename: Diana
authors.initials: D
authors.lastname: Casper
authors.forename: Mary T
authors.initials: MT
authors.lastname: Lucero
authors.forename: A Jane
authors.initials: AJ
authors.lastname: Roskams
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002461:Cell Line, Transformed; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology*; D002999:Clone Cells; D005260:Female; D005333:Fetus; D019922:GAP-43 Protein / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000378:metabolism; D018035:Receptors, Odorant / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D019922:GAP-43 Protein; D007473:Ion Channels; D019006:Neural Cell Adhesion Molecules; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D018035:Receptors, Odorant; D014157:Transcription Factors; D014404:Tubulin; D014212:Tretinoin; D019204:GTP-Binding Proteins