title: Lack of fibulin-3 alters regenerative tissue responses in the primary olfactory pathway.
abstract: The adult olfactory epithelium has maintained the ability to reconstitute its olfactory sensory neurons (OSNs) from a basal progenitor cell compartment. This allows for life-long turnover and replacement of receptor components as well as repair of the primary olfactory pathway in response to injury and environmental insults. The present study investigated whether fibulin-3, a glycoprotein in the extracellular matrix and binding partner of tissue inhibitor of metalloproteinases-3 (TIMP-3), plays a role in ongoing plasticity and regenerative events in the adult primary olfactory pathway. In wild-type control mice, fibulin-3 protein was detected on IB4(+)CD31(+) blood vessels, nerve fascicles and the basement membrane underneath the olfactory epithelium. After target ablation (olfactory bulbectomy), fibulin-3 was also abundantly present in the central nervous system (CNS) scar tissue that occupied the bulbar cavity. Using two different lesion models, i.e. intranasal Triton X-100 lesion and olfactory bulbectomy, we show that fibulin-3 deficient (Efemp1(-/-)) mice have impaired recovery of the olfactory epithelium after injury. Ten days post-injury, Efemp1(-/-) mice showed altered basal stem/progenitor cell proliferation and increased overall numbers of mature (olfactory marker protein (OMP) -positive) versus immature OSNs. However, compromised regenerative capacity of the primary olfactory pathway in Efemp1(-/-) mice was evidenced by reduced numbers of mature OSNs at the later time point of 42 days post-injury. In addition to these neural differences there were consistent changes in blood vessel structure in the olfactory lamina propria of Efemp1(-/-) mice. Overall, these data suggest a role for fibulin-3 in tissue maintenance and regeneration in the adult olfactory pathway.
authors.affiliation: School of Anatomy and Human Biology, The University of Western Australia, Crawley, Australia.
authors.forename: Jana
authors.initials: J
authors.lastname: Vukovic
authors.forename: Lihua Y
authors.initials: LY
authors.lastname: Marmorstein
authors.forename: Precious J
authors.initials: PJ
authors.lastname: McLaughlin
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Giles W
authors.initials: GW
authors.lastname: Plant
authors.forename: Alan R
authors.initials: AR
authors.lastname: Harvey
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Ruitenberg
mesh_terms: D000818:Animals; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009416:Nerve Regeneration / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000473:pathology / Q000502:physiology; D009831:Olfactory Mucosa / Q000166:cytology / Q000473:pathology / Q000502:physiology; D009833:Olfactory Pathways / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology
chemical_list: C492278:Efemp1 protein, mouse; D016326:Extracellular Matrix Proteins