Abstract:
Retinoic acid, a derivative of vitamin A, is known to play diverse roles in development
and regeneration. Previous research in the mollusc Lymnaea stagnalis has shown that a
gradient of all-trans retinoic acid attracts the growth cones of cultured neurons. The
present study investigates the sub-cellular mechanisms within the growth cones of
Lymnaea pedal A neurons which mediate the attractive response to a gradient of alltrans retinoic acid. In this study, the mechanism of growth cone turning is shown to be
local, as neurites mechanically isolated from their cell body retain the capacity to turn
towards an exogenous gradient of all-trans retinoic acid. The turning response is
dependent on the initiation of protein synthesis and calcium influx, but does not appear
to involve signaling through protein kinase C (PKC). The retinoid X receptor (RXR), which
classically functions as a transcription factor, was also shown to be involved in the
turning response, functioning locally through a non-genomic pathway. These data show,
for the first time in any species, that all-trans retinoic acid's chemotropic action involves
a local mechanism involving non-genomic signaling through the RXR. As retinoic acid is
known to playa role in regeneration, understanding the mechanisms underlying retinoic
acid signaling may lead to further advances in regenerative neuroscience.
