Versatile utilities of amphibians (part 4)

We have published the special issue “Versatile utilities of amphibians” in Part 1 (8 articles, Issue 6, 2022), Part 2 (3 articles, Issue 7, 2022), and Part 3 (5 articles, Issue 8, 2022) (see Michiue, Zorn, et al., 2022a, 2022b; Michiue, Kato, et al., 2022 for the previous Prefaces). Here, Part 4 is released with one research article and three short research articles. Konno (2023) focused on the metabolic transformation from ammonotelism to ureotelism during development in Xenopus laevis and found that simultaneous increase of urea cycle and gluconeogenetic enzymes' gene expression coincides with a corticoid surge occurring prior to metamorphosis. This finding may lead to understanding of the metabolic changes preceding metamorphosis, which may be closely related to the onset of the feeding and nutrient accumulation required for metamorphosis. Kondo et al. (2023) applied micro-CT (computed tomography) to analyze frog cortical bones and found that three Ceratophryidae species have porous cortical bones that is observed in reptiles, avians, and mammals. These data suggest that the process of fibrolamellar bone formation arose evolutionarily in amphibians. Further studies of the molecular mechanism of porous or non-porous bone formation in frogs may provide an evolutionary understanding of tetrapod bone structures. The molecular mechanism of amphibian metamorphosis is a longstanding question. Tanizaki et al. (2023) made a thyroid hormone receptor α (TRα) knockout (KO) frog using Xenopus tropicalis with the CRISPR/Cas9 genome editing technology. They performed chromatin immunoprecipitation-sequencing (ChIP-seq) to identify genes bound by TR in the tail of premetamorphic wild type or TRα KO tadpoles with or without T3 treatment, in comparison with the intestine and hindlimb. These ChIPseq datasets clearly showed tissue-specific roles in regulating T3-dependent metamorphosis by directly targeting the genes for metamorphosis, in which TRα is less important in tail regression duringmetamorphosis. Axis formation is a crucial step in establishing the body plan and amphibians have long been used as a model organism to study this. β-catenin protein stability is essential for axis formation and is regulated via canonical Wnt signaling. Goto and Shibuya (2023) analyzed the function and developmental role of the E3 ubiquitin ligase Maea (Macrophage erythroblast attacher) during early Xenopus laevis development. They found that Maea ubiquitinates β-catenin which leads to beta-catenin degradation through ubiquitination of yet identified sites, because β-catenin mutated in all four known ubiquitination Lys sites was still ubiquitinated and degraded by Maea. In addition, using lossand gain-of-function analyses, the data suggest that maea.L and maea.S homeologous genes contribute to head formation. Thus, they identified an additional new player for Xenopus head formation through ß-catenin degradation. Above are examples of the versatility of amphibian researches, comprising a classical subject (metabolic changes during development), a relatively classical analysis of a single gene in early development (the maea gene for head formation), a new technology for morphology (micro-CT and born structures), and a modern analysis using a combination of CRISPR/Cas9 genome editing and ChIP-seq (tissue-specific gene regulation for metamorphosis).