Lack of fibulin-3 alters regenerative tissue responses in the primary olfactory pathway

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 receptorcomponents as well as repair of the primary olfactory pathway in response to injury and environmentalinsults. The present study investigated whether fibulin-3, a glycoprotein in the extracellular matrix andbinding partner of tissue inhibitor of metalloproteinases-3 (TIMP-3), plays a role in ongoing plasticity andregenerative events in the adult primary olfactory pathway. In wild-type control mice, fibulin-3 protein wasdetected on IB4+CD31+ blood vessels, nerve fascicles and the basement membrane underneath the olfactoryepithelium. After target ablation (olfactory bulbectomy), fibulin-3 was also abundantly present in the centralnervous 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−/−) micehave impaired recovery of the olfactory epithelium after injury. Ten days post-injury, Efemp1−/− miceshowed altered basal stem/progenitor cell proliferation and increased overall numbers of mature (olfactorymarker protein (OMP) -positive) versus immature OSNs. However, compromised regenerative capacity of theprimary olfactory pathway in Efemp1−/− mice was evidenced by reduced numbers of mature OSNs at thelater time point of 42 days post-injury. In addition to these neural differences there were consistent changesin blood vessel structure in the olfactory lamina propria of Efemp1−/− mice. Overall, these data suggest a rolefor fibulin-3 in tissue maintenance and regeneration in the adult olfactory pathway. © 2009 Elsevier B.V. All rights reserved.