Zwilling-A and -B, Two Related Myelin Proteins of Teleosts, Which Originate from a Single Bicistronic Transcript

Abstract

Myelination, the ensheathment of axons by membranes of highly specialized glial cells, has been a crucial innovation during early vertebrate evolution. It enables high nerve signal conduction velocities, while maintaining nervous system size and energy requirements at moderate levels. Consequently, myelination has been conserved in all extant gnathostome vertebrates. In a genomewide mRNA expression screen, we identified several novel neural crest and myelin-specific transcripts in the zebrafish (Danio rerio). Here, we describe the characterization of two proteins, Zwilling-A and -B (ZwiA and ZwiB), which are exclusively expressed in myelinating glia of teleosts. They are structurally homologous and are translated from a common, bicistronic transcript. No similarities to sequences or domains of other proteins were detected. Analysis of phylogeny, genomic organization, and genomic syntenies suggests that the zwi gene has appeared soon after the teleost-specific genome duplication event and evolved under conservative selective pressure. We hypothesize that ZwiA and ZwiB serve important physiological functions in teleost myelin.

The scales and tales of myelination: using zebrafish and mouse to study myelinating glia

“…In both species, MBP and CNP comprise a large component of CNS myelin (Avila et al 2007, Möbius et al 2008). However, analyses of purified CNS myelin have identified several proteins that are abundant in zebrafish and other teleost species, but not detected in mammalian CNS myelin (Morris et al 2004, Schaefer and Brösamle 2008, Möbius et al 2008). For example, Zwilling-A and Zwilling-B are two related proteins that originate from a single bi-cistronic transcript and resemble the structure of Mbp, and both proteins are highly conserved throughout the teleost clade but absent from mammals (Schaefer and Brösamle 2008).…”

“…However, analyses of purified CNS myelin have identified several proteins that are abundant in zebrafish and other teleost species, but not detected in mammalian CNS myelin (Morris et al 2004, Schaefer and Brösamle 2008, Möbius et al 2008). For example, Zwilling-A and Zwilling-B are two related proteins that originate from a single bi-cistronic transcript and resemble the structure of Mbp, and both proteins are highly conserved throughout the teleost clade but absent from mammals (Schaefer and Brösamle 2008). Similarly, the protein 36K is a teleost-specific myelin protein that was first identified in trout myelin and has since been further characterized in zebrafish (Jeserich and Waehneldt 1986, Morris et al 2004).…”

Claudin k is specifically expressed in cells that form myelin during development of the nervous system and regeneration of the optic nerve in adult zebrafish

“…Developmental processes can be conveniently tracked using live imaging in zebrafish transgenic for fluorescent proteins, because embryos are transparent and develop externally. Due to their small size and availability in high numbers, zebrafish embryos and larvae are ideally suited for genetic and pharmacological screens (Haffter and N€ usslein-Volhard, 1996;Zon and Peterson, 2005), including screens for myelin-associated genes and altered myelination (Buckley et al, 2010;Pogoda et al, 2006;Schaefer and Br€ osamle, 2009;. Moreover, in contrast to mammals, adult zebrafish show a remarkably high capacity to regenerate neurons, for example in the retina (Bernardos et al, 2007;Fausett and Goldman, 2006;Fimbel et al, 2007) and the spinal cord (Reimer et al, 2008).…”

“…Gene expression corresponding to that of the proteolipid protein (PLP/DM20) has been detected in the CNS only (Br€ osamle and Halpern, 2002;Schweitzer et al, 2006;Yoshida and Macklin, 2005), whereas myelin basic protein (MBP), a protein essential for the initiation of myelin compaction, is found in both oligodendrocytes and Schwann cells (Br€ osamle and Halpern, 2002). The Zwilling-A and -B proteins are also expressed in both CNS and PNS and have been hypothesized to play roles in the adhesion of myelin lamellae in the zebrafish nervous system (Schaefer and Br€ osamle, 2009). Contactin1a (Cntn1/F3/F11), which plays a role in glial cell differentiation and myelination, is expressed in CNS and PNS of developing zebrafish, but in the adult becomes restricted to the optic axon layer in the retina, which contains only noncompact ''loose'' myelin (Schweitzer et al, 2007).…”

Genetic dissection of myelinated axons in zebrafish

“…Biochemical studies have described both similarities and differences between zebrafish and mammalian myelin. For example, Myelin basic protein (Mbp) and myelin proteolipid protein (PLP/DM20) are components of myelin in fish and mammals, but there are also teleost-specific myelin proteins in the CNS including 36K, Zwilling-A, and Zwilling-B [13,18–20]. Myelin Protein Zero (P 0 ), an Ig-like protein, is present in peripheral myelin of both tetrapods and teleosts, but only in fish is this protein prominently expressed in the CNS [13,21–23].…”