Odd-skipped family members have conserved roles in segmentation, appendage, excretory system and gut development in bilaterian animals

The odd-skipped related family of proteins are evolutionarily conserved zinc finger transcription factors in bilaterian animals with essential roles in body segmentation, as well as gut, excretory system and appendage development. Although they are prognostic biomarkers in several cancers, their molecular function is poorly understood. To gain a deeper understanding of how this family of transcription factors is implicated in human disorders and cancer, we explore the functions of Odd-skipped related transcription factors as well as their invertebrate homologs during development. We found that vertebrate Osr1 binds to DNA targets within the WNT, BMP, HH, TGFβ, Notch and retinoic acid signaling pathways, suggesting that Osr genes coordinate and integrate multiple pathways during development, potentially by binding to heterochromatin as pioneer transcription factors. From a protein tree analysis of odd-skipped family orthologs and paralogs, it appears that vertebrate, nematode, and insect paralogues have arisen via independent gene duplication events, and that their common ancestor likely had a single odd-family gene. We hypothesize that the ancestral odd-family protein was required for gut and gut-derived structures and was subsequently co-opted to perform additional functions in other tissues as part of the evolution of organisms. These observations posit new uncharacterized functions for Osr genes in the development of bilaterian animals and in cancer models.