Effects of intermediate filament disruption on the early development of the peripheral nervous system of Xenopus laevis.

The principal function of intermediate filaments is to strengthen cells. Their developmentally regulated, tissue-specific patterns of expression further suggest that they modulate cellular structural properties during development. To explore the role of intermediate filaments in development, we injected RNA encoding a truncated form of the Xenopus laevis middle-molecular-weight neurofilament protein (NF-M) into embryonic frog blastomeres at the 2-cell stage. A similar truncated form of mammalian NF-M disrupts neurofilaments (Type IV) and vimentin (Type III) intermediate filaments in transfected fibroblasts. In cultures made from dissociated neural tubes and their adjacent myotomes, the resultant protein disrupted both desmin filaments in muscle cells and neurofilaments in neurons during the first day of culture, which corresponds to stage 35/36 in the intact embryo. We next examined the effects of this truncated neurofilament protein on development of the nervous system. The greatest effects were seen on development of cranial and primary motor nerves, which were severely stunted as late as stage 37/38. In addition to these effects, ectopic neurons also appeared immediately beneath the epidermis along the flank of tadpoles expressing the truncated neurofilament protein. Whereas the former effects on peripheral nerve development were nearly identical to effects obtained with injected neurofilament antibodies, the ectopic neurons were novel, suggesting they resulted from the disruption of intermediate filaments other than the neurofilaments. These experiments thus implicate intermediate filaments in several functions important for normal neural development.