The signaling mechanisms and normal functions of the Nogo receptor will be investigated. Recent evidence indicates that the Nogo receptor (NogoR) signals by forming a complex with the p75 neurotrophin receptor (p75NTR). Uncharacterized structural homologs of both NogoR and p75NTR exist. It will be determined whether these homologs also form complexes and whether they signal similarly to the NogoR/p75NTR complex, via Nogo or MAG-dependent activation of RhoA and NF-kappaB. These studies will involve molecular cloning of mouse and zebrafish NogoR homologs, and expression in cultured mammalian cell lines of transfected NogoR, NogoR homolog, p75NTR and p75NTR homologs. Previous studies indicate that NogoR/p75NTR signaling functions to inhibit regeneration of the injured adult spinal cord. It is postulated that NogoR/p75NTR and homologs also function during embryonic development to guide neural axons to their appropriate targets. This hypothesis will be tested by employing morpholino-antisense RNA technology to disrupt expression of these proteins in zebrafish embryos. Effects of these manipulations on axonal targeting will be assessed by injecting the fluorescent marker Dil into embryos to allow microscopic imaging of axon trajectories.
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