Comp. Biochem. Physiol. Vol. 104B, No. 3, pp. 439-447, 1993 0305-0491/93 $6.00 + 0.00 Printed in Great Britain © 1993 Pergamon Press Ltd MINI REVIEW cDNA CLONES FROM FISH OPTIC NERVE ILANACOHEN and MICHALSCHWARTZ* Department of Neurobiology, The Weizmann Institute of Science, P.O. Box 26, 76100 Rehovot, Israel (Fax 972-8-344-131) (Received 3 August 1992; accepted 25 September 1992) Abstract--l. The present review describes the results of a cloning that was successfully employed in the study of optic nerve regeneration in fish. 2. Three intermediate filaments (IFs) expressed by the glial fish optic nerve were cloned. 3. By the use of this approach it was possible to resolve the controversial question of whether glial fibrillary acidic protein (GFAP) is expressed in the fish optic nerve. 4. Moreover, as a result of the information that emerged from the cloning, it was possible to raise well-characterized monospecific antibodies and successfully exploit them in order to determine glial cell maturation, lineage and plasticity, monitor the glial cell response to injury of the fish optic nerve, and compare it to that of a non-regenerative system. THE FISH OPTIC NERVE AS A MODEL FOR CENTRAL NERVOUS SYSTEM (CNS) REGENERATION The visual system is part of the CNS that in fish can regenerate spontaneously, unlike mammals (Sperry, 1948, Kiernan, 1979), and thus it serves as a useful model for the study of nerve injury and regeneration in the CNS (for reviews, see Graftstein, 1991; Sivron T. and Schwartz M., submitted). In the fish, all optic axons from each eye project to the contralateral lobe of the optic tectum. This provides a readily accessible pathway in which it is possible to produce lesions and study the resulting changes in the ganglion cells, axons and terminal fields. Axonal transport, cell body changes, influences of non-neuronal cells and changes in the synaptic target can be easily followed. Studies carried out in an attempt to uncover the reason for regeneration failure in the mammalian CNS have demonstrated that non-neuronal cells play a key role in determining the ability of a specific neuron to regenerate. CNS neurons in mammals are potentially capable of regeneration, but lack a per- missive and/or supportive environment (Ram6n y Cajal, 1959; Aguayo and David, 1981; Schwab and Thoenen, 1985; Kierstead et al., 1989). Another line of evidence comes from experiments which demon- strate that rabbit optic nerve axons have the potential to regenerate if their environment is suitably modified by the introduction of soluble substances derived from regenerating fish optic nerves (Schwartz et al., 1985; Lavie et al., 1990). Accordingly, it is feasible that fish CNS possesses the appropriate elements and machinery to render the environment of its injured *To whom correspondence should be addressed. axons permissive to and/or supportive of axonal regrowth. The non-neuronal environment of CNS neurons in vertebrates includes astrocytes, oligodendrocytes, res- ident microglia and blood-borne macrophages (Ra- m6n y Cajal, 1959; Stensaas, 1977; Murray, 1982). One or more combinations of these cellular elements and their response to axonal injury might contribute to the ability or inability of CNS neurons to regener- ate their injured axons. A comparison between the non-neuronal CNS environments in fish and mam- mals and their responses to axonal injury revealed similarities in some aspects, but profound differences in others. Attempts have been made to implicate these differences in the species-dependent ability of CNS neurons to regenerate. Until recently, little was known about the glial cell lineage in fish or the different subclasses of astrocytes and oligodendrocytes in the fish optic nerve. The rat optic nerve glial lineage is well characterized (Raft et al., 1983), and a comparison between fish and rat lineages might clarify the species-related differences in plasticity and ability to support axonal regeneration. The present review demonstrates the results, obtained by the cloning approach, in the direction of uncover- ing the glial cell lineage and plasticity during develop- ment and after axonal injury in the fish optic nerve model and comparing it to that of mammals. IFs AS MARKERS OF GLIAL CELLS Glial cells are characterized by their IFs. The type of IF that they express signifies their state of maturation. In addition, different cell types express different IFs (Lazarides, 1982). The following six 439