Abstract
The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7+/+ and α7lacZ/lacZ postnatal cerebral cortical neurons with α7+/+ or α7lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7+/+ OECs migrated through laminin-coated transwells compared to α7+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo.
Highlights
Olfactory ensheathing cells (OECs) are unique and highly specialized glia
We focused on the laminin receptor α7β1 integrin for three reasons: 1) α7 expression is reported in regions of the olfactory bulb (OB) that contain OECs [21]; 2) Schwann cells express α7, and many characteristics are shared between these two types of glial cells, including their regenerative properties [22, 23]; and 3) α7 in Schwann cells reportedly regulates peripheral neurite outgrowth and regeneration [24,25,26]
Using mice that express β-gal in lieu of α7 integrin, we show that α7/β-gal colocalizes with established OEC markers (SOX10, S100β, and Aquaporin 1 (AQP1)) but not with Olfactory marker protein (OMP), a marker for mature olfactory receptor neurons
Summary
Olfactory ensheathing cells (OECs) are unique and highly specialized glia. During embryonic development, OECs migrate with the axons of peripherally born olfactory receptor neurons (ORNs) into the olfactory nerve layer of the olfactory bulb. In addition to ensheathing ORN axons in the olfactory nerve and bulb, OECs interact with the glia limitans, i.e., the astrocytic barrier that normally isolates the central from the peripheral nervous system [3]. Because of their abilities to support adult neuronal growth and cross the PLOS ONE | DOI:10.1371/journal.pone.0153394. To investigate the role of α7 integrin in OECs, we inquired if the deletion of α7 would affect neurite outgrowth in an OEC-neuron co-culture model, and if adult OECs use α7 to mediate their migration on laminin Results from these experiments show that α7 integrin is a key-signaling molecule involved in the migration of OECs on a laminin matrix
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