Retinoids in development and regeneration in the CNS of vertebrates and invertebrates

ABSTRACT

Retinoic acid (RA) is a biologically important metabolite of vitamin A that modulates growth and differentiation of many cell types. Although abundant in the CNS of many vertebrates, the precise role of RA in neural development has yet to be elucidated. Moreover, very little information is available regarding the role of RA in invertebrate neural development and regeneration. We have recently demonstrated that RA stimulates neurite outgrowth from adult newt spinal cord explants and may represent a significant factor in vivo in the reciprocal interactions between peripheral nerves and regenerating limb blastema cells. This interaction leads to the restoration of a functional limb after amputation. In support of this model, we have cloned a cDNA for the retinoic acid receptor of the β subtype (RARβ) whose expression is restricted to the spinal cord and brain of the adult newt and may be present in the limb blastema. This receptor may mediate the trophic effects of blastema-derived RA on neurite outgrowth and chemotaxis from spinal cord neurons. We have also extended our studies on the role of RA to the simple nervous system of the mollusc, Lymnaea stagnalis. Preliminary data support a role for RA in the survival, outgrowth, and chemotactic response of single, isolated, identifiable neurons in culture. This work represents the first evidence for chemotaxis and trophic effects of retinoids in an invertebrate nervous system. It is hoped that our work will shed light on the evolutionary conservation of a role for RA in neural development and regeneration.