Work

Protogenin facilitates trunk-to-tail HOX code transition via modulating GDF11/SMAD2 signaling in mammalian embryos

Year: 2024

Type: article

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. Protogenin regulates vertebral axial patterning in mammalian embryos by interacting with GDF11, enhancing GDF11/pSMAD2 signaling to facilitate trunk-to-tail HOX code transition and ensure proper expression of posterior HOX genes.

Source: Communications Biology

DOI: 10.1038/s42003-024-07342-8