XEFILTIN, A XENOPUS-LAEVIS NEURONAL INTERMEDIATE FILAMENT PROTEIN, ISEXPRESSED IN ACTIVELY GROWING OPTIC AXONS DURING DEVELOPMENT AND REGENERATION

Neurofilaments are an important structural component of the axonal cyt oskeleton and are made of neuronal intermediate filament (nIF) protein s. During axonal development, neurofilaments undergo progressive chang es in molecular composition. In mammals, for example, highly phosphory lated forms of the middle-and high-molecular-weight neurofilament prot eins (NF-M and NF-H, respectively) are characteristic of mature axons, whereas nIF proteins such as alpha-internexin are typical of young ax ons. Such changes have been proposed to help growing axons accommodate varying demands for plasticity and stability by modulating the struct ure of the axonal cytoskeleton. Xefiltin is a recently discovered nIF protein of the frog Xenopus laevis, whose nervous system has a large c apacity for regeneration and plasticity. By amino acid identity, xefil tin is closely related to two other nIF proteins, alpha-internexin and gefiltin. alpha-Internexin is found principally in embryonic axons of the mammalian brain, and gefiltin is expressed primarily in goldfish retinal ganglion cells and has been associated with the ability of the goldfish optic nerve to regenerate. Like gefiltin in goldfish, xefilt in in Xenopus is the most abundantly expressed nIF protein of mature r etinal ganglion cells. In the present study, we used immunocytochemist ry to study the distribution of xefiltin during optic nerve developmen t and regeneration. During development, xefiltin was found in optic ax ons at stage 35/36, before they reach the tectum at stage 37/38. Simil arly, after an orbital crush injury, xefiltin first reemerged in optic axons after the front of regeneration reached the optic chiasm, but b efore it reached the tectum. Thus, during both development and regener ation, xefiltin was present within actively growing optic axons. In ad dition, aberrantly projecting retinoretinal axons expressed less xefil tin than those entering the optic tract, suggesting that xefiltin expr ession is influenced by interactions between regenerating axons and ce lls encountered along the visual pathway. These results support the id ea that changes in xefiltin expression, along with those of other nIF proteins, modulate the structure and stability of actively growing opt ic axons and that this stability is under the control of the pathway w hich growing axons follow. (C) 1997 John Wiley & Sons, Inc.