FGF-2 up-regulation and proliferation of neural progenitors in the regenerating amphibian spinal cord in vivo

Regeneration of the spinal cord occurs spontaneously in adult urodele amphi bians. The key cells in this regenerative process appear to be the ependyma l cells that following injury migrate and proliferate to form the ependymal tube from which the spinal cord regenerates. Very little is known about th e signal(s) that initiates and maintains the proliferative response of thes e cells. Fibroblast growth factor 2 (FGF 2) has been shown to play a role i n maintaining neural progenitor cell cycling in vitro and may be important for neuronal survival and axonal growth after injury. We have investigated its role in regeneration of the spinal cord in vivo following tail amputati on in the adult salamander, Pleurodeles wa1t1. We show that only the low-mo lecular-weight form of FGF-2 is found in Pleurodeles and that in the normal cord it is expressed in a subset of neurons, but is hardly detectable in e pendymal cells. Tail amputation results in induction of FGF-2 in the ependy mal cells of the regenerating structure, and later in regeneration FGF-2 is up-regulated in some newborn neurons. FGF-2 pattern of expression in the e pendymal tube parallels that of proliferation. Furthermore, exogenous FGF-2 significantly increases ependymal cell proliferation in vivo. Overall our results strongly support the view that one important role of FGF-2 during s pinal cord regeneration in Pleurodeles is to induce proliferation of neural progenitor cells. (C) 2000 Academic Press.