Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos
Abstract During embryogenesis, vertebral axial patterning is intricately regulated by multiple signaling networks. This study elucidates the role of protogenin (Prtg), an immunoglobulin superfamily member, in vertebral patterning control. Prtg knockout (Prtg − / − ) mice manifest anterior homeotic t...
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07342-8 |
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| author | Yu-Sheng Hung Wei-Mi Lin Yu-Chiuan Wang Wei-Chih Kuo Yu-Yang Chen Ming-Ji Fann Jenn-Yah Yu Yu-Hui Wong |
| author_facet | Yu-Sheng Hung Wei-Mi Lin Yu-Chiuan Wang Wei-Chih Kuo Yu-Yang Chen Ming-Ji Fann Jenn-Yah Yu Yu-Hui Wong |
| author_sort | Yu-Sheng Hung |
| collection | DOAJ |
| description | Abstract During embryogenesis, vertebral axial patterning is intricately regulated by multiple signaling networks. This study elucidates the role of protogenin (Prtg), an immunoglobulin superfamily member, in vertebral patterning control. Prtg knockout (Prtg − / − ) mice manifest anterior homeotic transformations in their vertebral columns and significant alterations in homeobox (Hox) gene expression. Transcriptomic profiling of Prtg − / − mouse embryos highlights Prtg-regulated genes involved in axial development, particularly within the transforming growth factor beta (TGFβ) signaling pathway. Reduced TGFβ signaling in Prtg − / − mouse embryos is evidenced by decreased phosphorylated Smad2 (pSmad2) levels and its downstream target genes in the developing tail. We further show that Prtg interacts with growth differentiation factor 11 (GDF11) to enhance GDF11/pSmad2 signaling activity. Using human-induced pluripotent stem cell-derived presomitic mesoderm-like (hiPSC-PSM) cells, we demonstrate delayed posterior HOX gene expression upon PRTG knockout, which is rescued by GDF11 supplementation. These findings provide compelling evidence that PRTG regulates HOX genes through the GDF11/SMAD2 signaling pathway. |
| format | Article |
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| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
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| series | Communications Biology |
| spelling | doaj-art-d71f48664b844eafbac55285120fe9c52025-08-20T02:31:55ZengNature PortfolioCommunications Biology2399-36422024-12-017111610.1038/s42003-024-07342-8Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryosYu-Sheng Hung0Wei-Mi Lin1Yu-Chiuan Wang2Wei-Chih Kuo3Yu-Yang Chen4Ming-Ji Fann5Jenn-Yah Yu6Yu-Hui Wong7Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityInstitute of Neuroscience, College of Life Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityBrain Research Center, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityDepartment of Life Sciences and Institute of Genome Sciences, College of Life Sciences, National Yang Ming Chiao Tung UniversityAbstract During embryogenesis, vertebral axial patterning is intricately regulated by multiple signaling networks. This study elucidates the role of protogenin (Prtg), an immunoglobulin superfamily member, in vertebral patterning control. Prtg knockout (Prtg − / − ) mice manifest anterior homeotic transformations in their vertebral columns and significant alterations in homeobox (Hox) gene expression. Transcriptomic profiling of Prtg − / − mouse embryos highlights Prtg-regulated genes involved in axial development, particularly within the transforming growth factor beta (TGFβ) signaling pathway. Reduced TGFβ signaling in Prtg − / − mouse embryos is evidenced by decreased phosphorylated Smad2 (pSmad2) levels and its downstream target genes in the developing tail. We further show that Prtg interacts with growth differentiation factor 11 (GDF11) to enhance GDF11/pSmad2 signaling activity. Using human-induced pluripotent stem cell-derived presomitic mesoderm-like (hiPSC-PSM) cells, we demonstrate delayed posterior HOX gene expression upon PRTG knockout, which is rescued by GDF11 supplementation. These findings provide compelling evidence that PRTG regulates HOX genes through the GDF11/SMAD2 signaling pathway.https://doi.org/10.1038/s42003-024-07342-8 |
| spellingShingle | Yu-Sheng Hung Wei-Mi Lin Yu-Chiuan Wang Wei-Chih Kuo Yu-Yang Chen Ming-Ji Fann Jenn-Yah Yu Yu-Hui Wong Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos Communications Biology |
| title | Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos |
| title_full | Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos |
| title_fullStr | Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos |
| title_full_unstemmed | Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos |
| title_short | Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos |
| title_sort | protogenin facilitates trunk to tail hox code transition via modulating gdf11 smad2 signaling in mammalian embryos |
| url | https://doi.org/10.1038/s42003-024-07342-8 |
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