Expanding the Evo-Devo Toolkit: Generation of 3D mammary tissue from diverse mammals

Abstract

The divergent events during mammary gland development between species and across evolution are not well studied mainly due to the lack of tractable model systems. In theory, advancements in the field of organoid technology now make it possible to study developmental processes adapted throughout species evolutions to accommodate advantageous phenotypes. However, its application to the mammary gland remains limited to rodents and humans. In the current study, we successfully created next-generation 3D mammary gland organoids from eight eutherian mammals and the first 3D organoid of a marsupial mammary gland (the gray short-tailed opossum), representing a more ancient version of the mammary gland. Using mammary organoids, we identified a role for ROCK protein in regulating branching morphogenesis, a role that manifests differently in human and opossum mammary organoids. This finding demonstrates the utility of 3D organoid model for understanding the evolution and adaptations of signaling pathways. Overall, the establishment of mammary organoids as animal model surrogates is a significant advancement in the field of mammary gland biology and evolution and paves the way for future studies utilizing this model. This achievement highlights the potential of organoid models to expand our understanding of mammary gland biology and evolution and their utility in studying milk production and breast cancer research.