Conditionally immortalized clonal cell lines from the mouse olfactory placode differentiate into olfactory receptor neurons.
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.
Illing
Nicola
N
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, V5Z 4H4.
Boolay
Sihaam
S
Siwoski
Jenny S
JS
Casper
Diana
D
Lucero
Mary T
MT
Roskams
A Jane
AJ
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
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