VITRONECTIN IS EXPRESSED IN THE VENTRAL REGION OF THE NEURAL-TUBE ANDPROMOTES THE DIFFERENTIATION OF MOTOR-NEURONS

The extracellular matrix protein vitronectin and its mRNA are present in the embryonic chick notochord, floor plate and in the ventral neura l tube at the time position of motor neuron generation. When added to cultures of neural tube explants of developmental stage 9, vitronectin promotes the generation of motor neurons in the absence of either not ochord or exogenously added Sonic hedgehog. Conversely, the neutralisa tion of endogenous vitronectin with antibodies inhibits over 90% motor neuron differentiation in co-cultured neural tube/notochord explants, neural tube explants cultured in the presence of Sonic hedgehog, and in committed (stage 13) neural tube explants. Furthermore, treatment o f embryos with anti-vitronectin antibodies results in a substantial an d specific reduction in the number of motor neurons generated in vivo. These results demonstrate that vitronectin stimulates the differentia tion of motor neurons in vitro and in vivo. Since the treatment of sta ge 9 neural tube explants with Sonic hedgehog resulted in induction of vitronectin mRNA expression before the expression of floor plate mark ers, we conclude that vitronectin may act either as a downstream effec tor in the signalling cascade induced by Sonic hedgehog, or as a syner gistic factor that increases Shh-induced motor neuron differentiation.