Microtubule-associated protein tau promotes neuronal class II β-tubulin microtubule formation and axon elongation in embryonic Xenopus laevis

Compared with its roles in neurodegeneration, much less is known about microtubule-associated protein tau's normal functions in vivo, especially during development. The external development and ease of manipulating gene expression of Xenopus laevis embryos make them especially useful for studying gene function during early development. To study tau's functions in axon outgrowth, we characterized the most prominent tau isoforms of Xenopus embryos and manipulated their expression. None of these four isoforms were strictly analogous to those commonly studied in mammals, as all constitutively contained exon 10, which is preferentially removed from mammalian fetal tau isoforms, as well as exon 8, which in mammals is rare. Nonetheless, like mammalian tau, Xenopus tau exhibited alternative splicing of exon 4a, which in mammals distinguishes 'big' tau of peripheral neurons, and exon 6. Strongly suppressing tau expression with antisense morpholino oligonucleotides only modestly compromised peripheral nerve outgrowth of intact tadpoles, but severely disrupted neuronal microtubules containing class II β-tubulins while leaving other microtubules largely unperturbed. Thus, the relatively mild dependence of axon development on tau likely resulted from having only a single class of microtubules disrupted by its loss. Also, consistent with its greater expression in long peripheral axons, boosting expression of 'big' tau increased neurite outgrowth significantly and enhanced tubulin acetylation more so than did the smaller isoform. These data demonstrate the utility of Xenopus as a tool to gain new insights into tau's functions in vivo.