Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb

Abstract

New subventricular zone (SVZ)-derived neuroblasts that migrate via the rostral migratory stream are continuously added to the olfactory bulb (OB) of the adult rodent brain. Anosmin-1 (A1) is an extracellular matrix protein that binds to FGF receptor 1 (FGFR1) to exert its biological effects. When mutated as in Kallmann syndrome patients, A1 is associated with severe OB morphogenesis defects leading to anosmia and hypogonadotropic hypogonadism. Here, we show that A1 over-expression in adult mice strongly increases proliferation in the SVZ, mainly with symmetrical divisions, and produces substantial morphological changes in the normal SVZ architecture, where we also report the presence of FGFR1 in almost all SVZ cells. Interestingly, for the first time we show FGFR1 expression in the basal body of primary cilia in neural progenitor cells. Additionally, we have found that A1 over-expression also enhances neuroblast motility, mainly through FGFR1 activity. Together, these changes lead to a selective increase in several GABAergic interneuron populations in different OB layers. These specific alterations in the OB would be sufficient to disrupt the normal processing of sensory information and consequently alter olfactory memory. In summary, this work shows that FGFR1-mediated A1 activity plays a crucial role in the continuous remodelling of the adult OB.

Olfactory bulb plasticity ensures proper olfaction after severe impairment in postnatal neurogenesis

“…To determine both the olfactory detection threshold and the olfactory discrimination of mice, custom-built, computer-controlled, six-channel air-dilution olfactometers were employed, based on previous models 66, 67 . The functioning of such devices was based on electronic valves controlling purified air streams, which were passed through mineral oil with diluted odorants (see supplementary material).…”

Prdx1 Promotes the Loss of Primary Cilia in Esophageal Squamous Cell Carcinoma

“…Studies have shown that FGFR1 knockout can cause ciliary shortening (24,25), IGFR1 plays an important role in ciliary elongation (26,27), and ABI2 is a tumor suppressor and a cell migration suppressor, participating in human head and neck squamous cell carcinoma (28). And NEDD9 and Aurora A was also known as important oncogenes regulating, correspondingly, cell division and cell invasion (29)(30)(31)(32).…”

Primary Cilia and Coordination of Receptor Tyrosine Kinase (RTK) and Transforming Growth Factor β (TGF-β) Signaling

“…Functional links to cilia have also been reported for fibroblast growth factor receptors (FGFRs), which seem to regulate ciliogenesis by promoting transcription of ciliogenic genes . Further, FGFRs were reported to localize to motile cilia in the airways of the rhesus monkey (Evans et al 2002) as well as to the basal body of primary cilia in mouse neural progenitor cells (Garcia-Gonzalez et al 2016). Finally, angiopoietin receptors Tie1 and Tie2 were shown to localize to cilia of the murine female reproductive organs, including primary cilia of the surface epithelium of the ovary, bursa, and extraovarian rete ducts, as well as to motile cilia of the oviduct .…”