Xenopus laevis peripherin (XIF3) is expressed in radial glia and proliferating neural epithelial cells as well as in neurons

Abstract

Neuronal intermediate filament (nIF) proteins form the most abundant component of the axonal cytoskeleton. Thus, understanding their function and the regulation of their expression is essential for comprehending how axonal structure is regulated. Although most vertebrate nIF proteins are classified as type IV intermediate filament (IF) proteins, additional nIF proteins exist in frogs (Xenopus laevis), cyprinid fishes, and mammals (called XIF3, plasticin, and peripherin, respectively) that are classified as type III. Expression of a type III nIF protein is correlated strongly with the earliest phases of axonal outgrowth in fishes but less so in mammals. To understand better how the correlation between type III nIF protein expression and early phases of axonal outgrowth has changed during evolution, the authors examined XIF3 expression in Xenopus laevis. In Xenopus, the association between XIF3 expression and early axonal outgrowth was especially strong. For example, during early axonal development, XIF3 expression preceded and was more abundant and widespread than that of any of the type IV nIF proteins. As axons matured, neuronal expression of XIF3 gradually became more restricted while that of type IV nIF proteins increased. These results support the idea that type III nIF proteins play a special role during early phases of axonal outgrowth. In addition to finding XIF3 in neurons, the authors also unexpectedly found it in regions of the central nervous system that contain proliferating cells and radial glia. As a framework for interpreting variations in nIF expression in different vertebrate species, the authors built phylogenetic trees to clarify relationships among vertebrate nIF proteins. These trees supported the classification of XIF3, plasticin, and peripherin as orthologs (products of the same genetic locus, evolving separately only since the species lineages diverged). Thus, XIF3, plasticin, and peripherin probably should be referred to as Xenopus, fish, and mammalian peripherin, respectively. This finding argues that differences in expression of these three proteins in frogs, fishes, and mammals are the result of regulatory changes to the peripherin ancestral gene along each lineage. The expression of a peripherin ortholog in Xenopus glia may represent either an adaptation that arose since the divergence of Xenopus from mammals or, alternatively, a feature retained from an ancestral IF protein that was expressed originally both in neurons and in glia.

Müller glia reactivity follows retinal injury despite the absence of the glial fibrillary acidic protein gene in Xenopus

“…5G). prph expression is most abundantly detected in newly born ganglion and other retinal cells adjacent to the CMZ, consistent with previous findings (Gervasi et al, 2000). Transcripts were also detected at the inner and outer plexiform layers of the peripheral retina (Fig.…”

“…5H). Expression was also observed in the dorsal root ganglia (not shown, and Gervasi et al, 2000). In the brain, prph transcripts appeared restricted to cells of the ventricular zone (Fig.…”

“…Polyclonal antibodies generated in two rabbits using the same X. laevis Prph C-terminal peptide both detected myc-XlaPrph, but no other IFP tested (Fig. 4C and D; Gervasi et al, 2000). Similarly, a mouse monoclonal antibody (14h7) generated using extracts of the X. laevis A6 kidney epithelial cell line as an immunogen and later shown to detect vimentin, detected myc-XlaVim, but none of other IFPs tested (Fig.…”

“…Prph is an interesting candidate because in mammals and zebrafish, it is only expressed in neurons (Fuchs and Weber, 1994; McLenachan et al, 2008), while Xenopus Prph is expressed in neurons, proliferating cells as well as glia (Gervasi et al, 2000). In mammals, peripherin is abundant in PNS neurons and is also expressed in RGCs (McLenachan et al, 2008; Wang et al, 2007).…”

“…The expression patterns of X. laevis and mammalian prph however, are distinct. While both Xenopus and mouse prph are expressed in axon-elaborating postmitotic neurons, Xenopus prhp is also expressed in radial glia and in regions of the nervous system actively proliferating (Gervasi et al, 2000). The transcriptional expression pattern of Xenopus gfap has not been reported.…”