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In this study, we investigate the role of the homeologous <jats:italic>uncx.L<\/jats:italic> and <jats:italic>uncx.S<\/jats:italic> genes in the vertebral column morphogenesis of the allotetraploid frog <jats:italic>Xenopus laevis<\/jats:italic>. We initiated our study by cloning the <jats:italic>uncx<\/jats:italic> orthologous genes in the anuran <jats:italic>Xenopus<\/jats:italic> and determining their spatial expression patterns using <jats:italic>in situ<\/jats:italic> hybridization. Additionally, we employed gain\u2010of\u2010function and loss\u2010of\u2010function approaches through dexamethasone\u2010inducible <jats:italic>uncx<\/jats:italic> constructs and antisense morpholino oligonucleotides, respectively. Comparative analysis of the messenger RNA sequences of homeologous <jats:italic>uncx<\/jats:italic> genes revealed that the <jats:italic>uncx.L<\/jats:italic> variant lacks the eh1\u2010like repressor domain. Our spatial expression analysis indicated that in the presomitic mesoderm and somites, the transcripts of <jats:italic>uncx.L<\/jats:italic> and <jats:italic>uncx.S<\/jats:italic> are located in overlapping domains. Alterations in the function of <jats:italic>uncx<\/jats:italic> genes significantly impact the development and differentiation of the sclerotome and myotome, resulting in axial skeleton malformations. Our findings suggest a scenario where the homeologous genes <jats:italic>uncx.L<\/jats:italic> and <jats:italic>uncx.S<\/jats:italic> exhibit antagonistic functions during somitogenesis. Specifically, <jats:italic>uncx.S<\/jats:italic> appears to be crucial for sclerotome development and differentiation, while <jats:italic>uncx.L<\/jats:italic> primarily influences myotome development. Postallotetraploidization, the <jats:italic>uncx.L<\/jats:italic> gene in <jats:italic>X. laevis<\/jats:italic> evolved to lose its eh1\u2010like repressor domain, transforming into a \u201cnative dominant negative\u201d variant that potentially competes with <jats:italic>uncx.S<\/jats:italic> for the same target genes. Finally, the histological analysis revealed that <jats:italic>uncx.S<\/jats:italic> expression is necessary for the correct formation of pedicles and neural arch of the vertebrae, and <jats:italic>uncx.L<\/jats:italic> is required for trunk muscle development.<\/jats:p>","DOI":"10.1002\/jez.b.23235","type":"journal-article","created":{"date-parts":[[2023,12,29]],"date-time":"2023-12-29T06:59:50Z","timestamp":1703833190000},"page":"350-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antagonistic regulation of homeologous <i>uncx.L<\/i> and <i>uncx.S<\/i> genes orchestrates myotome and sclerotome differentiation in the evolutionarily divergent vertebral column of <i>Xenopus laevis<\/i>"],"prefix":"10.1002","volume":"342","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-7717","authenticated-orcid":false,"given":"Romel S.","family":"S\u00e1nchez","sequence":"first","affiliation":[{"name":"Instituto Superior de Investigaciones Biol\u00f3gicas (INSIBIO), CONICET and Instituto de Biolog\u00eda \u201cDr. Francisco D. Barbieri Facultad de Bioqu\u00edmica, Qu\u00edmica y Farmacia, Universidad Nacional de Tucum\u00e1n San Miguel de Tucum\u00e1n Argentina"},{"name":"C\u00e1tedra de Biolog\u00eda General Facultad de Ciencias Naturales e Instituto Miguel Lillo, Universidad Nacional de Tucum\u00e1n San Miguel de Tucum\u00e1n Argentina"},{"name":"C\u00e1tedra de Fisiolog\u00eda, Departamento Biom\u00e9dico Facultad de Medicina, Universidad Nacional de Tucum\u00e1n San Miguel de Tucum\u00e1n Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda A","family":"Lazarte","sequence":"additional","affiliation":[{"name":"Instituto de Biodiversidad Neotropical (IBN), CONICET Facultad de Ciencias Naturales e IML, Universidad Nacional de Tucum\u00e1n Yerba Buena Tucum\u00e1n Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia S. L.","family":"Abdala","sequence":"additional","affiliation":[{"name":"C\u00e1tedra de Biolog\u00eda General Facultad de Ciencias Naturales e Instituto Miguel Lillo, Universidad Nacional de Tucum\u00e1n San Miguel de Tucum\u00e1n Argentina"},{"name":"Instituto de Biodiversidad Neotropical (IBN), CONICET Facultad de Ciencias Naturales e IML, Universidad Nacional de Tucum\u00e1n Yerba Buena Tucum\u00e1n Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara S.","family":"S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Instituto Superior de Investigaciones Biol\u00f3gicas (INSIBIO), CONICET and Instituto de Biolog\u00eda \u201cDr. Francisco D. 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