Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb

Abstract

The adult brain subventricular zone (SVZ) produces neuroblasts that migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB) in a specialized niche. Galectin-3 (Gal-3) regulates proliferation and migration in cancer and is expressed by activated macrophages after brain injury. The function of Gal-3 in the normal brain is unknown, but we serendipitously found that it was expressed by ependymal cells and SVZ astrocytes in uninjured mice. Ependymal cilia establish chemotactic gradients and astrocytes form glial tubes, which combine to aid neuroblast migration. Whole-mount preparations and electron microscopy revealed that both ependymal cilia and SVZ astrocytes were disrupted in Gal3−/− mice. Interestingly, far fewer new BrdU+ neurons were found in the OB of Gal3−/− mice, than in wild-type mice 2 weeks after labeling. However, SVZ proliferation and cell death, as well as OB differentiation rates were unaltered. This suggested that decreased migration in vivo was sufficient to decrease the number of new OB neurons. Two-photon time-lapse microscopy in forebrain slices confirmed decreased migration; cells were slower and more exploratory in Gal3−/− mice. Gal-3 blocking antibodies decreased migration and dissociated neuroblast cell–cell contacts, whereas recombinant Gal-3 increased migration from explants. Finally, we showed that expression of phosphorylated epidermal growth factor receptor (EGFR) was increased in Gal3−/− mice. These results suggest that Gal-3 is important in SVZ neuroblast migration, possibly through an EGFR-based mechanism, and reveals a role for this lectin in the uninjured brain.

Immunohistochemical localization of galectin-3 in the brain with Theiler's murine encephalomyelitis virus (DA strain) infection

“…2A) immunostaining was observed in some ependymal cells ( Fig. 2A, arrows) and lining ventricles, as shown previously [3], but not in neurons and glial cells. In TMEV-infected brains at day 7 post-infection ( Fig.…”

“…Even though the expression of galectin-3 is very low in other glial cells, astrocytes and ependymal cells have been suggested as another candidate for galectin-3 expression in the Junin-virus-infected mouse brain [6] and normal CNS development [3], respectively. In the present study, we confirmed that galectin-3 was mainly found in macrophages/activated microglia, but not in ramified Iba-1-positive microglia, in acute (day 7 post-infection) and chronic (day 81 post-infection) TMEV infection.…”

“…Besides the biological role of galectin-3 in normal tissues, it plays pleitrophic roles in the course of inflammation through the facilitation of cell migration and activation [1,22,23]. Although some studies have shown that galectin-3 is not expressed in normal central nervous system (CNS) tissues [18], more recent work has reported galectin-3 expression by ependymal cells and astrocytes from the subventricular zone in normal uninjured mice [3], a process in which ependymal cilia establish chemotactic gradients and astrocytes form glial tubes, which combine to aid neuroblast migration [3]. Galectin-3 has also been shown to drive oligodendrocyte differentiation [17].…”

Galectin-3 Is Required for Resident Microglia Activation and Proliferation in Response to Ischemic Injury

“…Furthermore, studies from Compte et al (2011) reported potential role of galectin-3 in the modulation of cell motility in the rostral migratory stream. While galectin-3 is abundant activated microglia (Kriz et al, 2003;Lalancette-Hébert et al, 2007;Ohtaki et al, 2008;Comte et al, 2011;Satoh et al, 2011), resting cells do not express galectin-3 and consequently there is no overt microglial phenotype in galectin-3-deficient mice in normal conditions (Figs. 1, 2).…”

Time-lapse Imaging of Neuroblast Migration in Acute Slices of the Adult Mouse Forebrain

“…These differences in acquisition parameters are likely to underlie the discrepancies in the speeds of neuroblasts migration reported by different groups. By performing rapid acquisitions with a 15-30 sec interval and determining the rate of migration exclusively during the migration phases, we calculated a speed of migration of 120-150 μm/h 4,12 , whereas other groups, who use an acquisition interval of 3-7 min reported a speed of 50-100 μm/h 14,15,18 . The main drawback of wide-field fluorescent imaging with CCD cameras is that it provides lower spatial resolution than scanning systems.…”