The role of neural crest cells in olfactory/terminal nerve and GnRH neuron development. (360G-Wellcome-091555_Z_10_Z)

Throughout life, olfactory ensheathing cells (OECs) promote axon-sprouting from olfactory-receptor neurons (ORNs) and guide them to their targets in the olfactory bulbs. These properties mean OECs are intensively studied as therapeutic agents for transplant-mediated spinal cord repair, but how they act to promote functional recovery remains unclear. Mounting evidence suggests OECs also promote entry into the embryonic forebrain of olfactory/terminal-nerve axons and gonadotropin-releasing-hormone neurons: failure of these events causes anosmia and sterility (Kallmann s syndrome; KS). We have recently found that OECs are derived from the neural crest, and not from the olfactory placodes as current dogma holds. This opens up new possibilities for elucidating the mechanisms underlying the interactions of OECs with axons and other cells. By analysing mutant mouse embryos, and using recently-developed conditional in ovo electroporation techniques, we will (1) investigate the requirement for OECs for olfactory/terminal axon and GnRH neuron entry into the forebrain; (2) test hypotheses about three potential underlying molecular mechanisms: FGF signalling, matrix-metalloprotease secretion and Wnt signalling. A better understanding of the molecular basis of OEC interactions with other cells and axons should shed new light on KS, and potentially also on the mechanisms by which OECs promote spinal cord repair.