title: Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons.
abstract: Odorant receptors (OR) are strongly implicated in coalescence of olfactory sensory neuron (OSN) axons and the formation of olfactory bulb (OB) glomeruli. However, when ORs are first expressed relative to basal cell division and OSN axon extension is unknown. We developed an in vivo fate-mapping strategy that enabled us to follow OSN maturation and axon extension beginning at basal cell division. In parallel, we mapped the molecular development of OSNs beginning at basal cell division, including the onset of OR expression. Our data show that ORs are first expressed around 4 d following basal cell division, 24 h after OSN axons have reached the OB. Over the next 6+ days the OSN axons navigate the OB nerve layer and ultimately coalesce in glomeruli. These data provide a previously unidentified perspective on the role of ORs in homophilic OSN axon adhesion and lead us to propose a new model dividing axon extension into two phases. Phase I is OR-independent and accounts for up to 50% of the time during which axons approach the OB and begin navigating the olfactory nerve layer. Phase II is OR-dependent and concludes as OSN axons coalesce in glomeruli.
authors.affiliation: Departments of Neurosurgery.
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Rodriguez-Gil
authors.affiliation: Departments of Neurosurgery.
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Bartel
authors.affiliation: Departments of Neurosurgery.
authors.forename: Austin W
authors.initials: AW
authors.lastname: Jaspers
authors.affiliation: Departments of Neurosurgery.
authors.forename: Arie S
authors.initials: AS
authors.lastname: Mobley
authors.affiliation: Departments of Neurosurgery.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Imamura
authors.affiliation: Departments of Neurosurgery, Neurobiology, and The Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06520-8082 charles.greer@yale.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Greer
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation; D002465:Cell Movement; D018274:Electroporation; D019922:GAP-43 Protein / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D009832:Olfactory Nerve / Q000166:cytology; D018034:Olfactory Receptor Neurons / Q000378:metabolism; D018035:Receptors, Odorant / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D012903:Smell / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D013629:Tamoxifen / Q000737:chemistry
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D019922:GAP-43 Protein; D018035:Receptors, Odorant; D013629:Tamoxifen; C499317:Ascl1 protein, mouse
keywords: Ascl1; axon guidance; olfactory epithelium; olfactory marker protein; tamoxifen