The recent discovery of a proteolipid protein gene family has revealed that its members are in fact widely distributed and are not exclusively associated with myelination. To date, three different gene products, DMโฃ/DM-20/PLP, DMโค/M6a, and DMโฅ/M6b, have been isolated from certain primitive fish species, mouse, and human central nervous system (CNS). We cloned Xenopus laevis orthologues of DMโค/M6a and DMโฅ/M6b and investigated the expression patterns of these gene transcripts as well as that of PLP in developing Xenopus CNS. As is the case in shark and mouse, the mRNA encoding the major myelin integral protein, PLP, is first detected at stage 42/43 in tadpoles and is exclusively found in morphologically recognizable oligodendrocytes throughout the brain, while DMโค mRNA is solely expressed in young presumptive neurons in the gray matter. There exist two distinct DMโฅ mRNAs and, in contrast to these evolutionarily conserved expression patterns, DMโฅ mRNAs distribute uniquely within the ventricular zone in young tadpoles (stage 25) through maturity. Furthermore, both DMโค and DMโฅ are expressed in the developing retina, and their distributions are different from one other. In Xenopus CNS, therefore, the expression patterns of three proteolipid proteins, PLP, DMโค, and DMโฅ, are distinct from each other, implying very different roles for their protein products within the cell populations in which they are expressed.