Fused in sarcoma (FUS) inhibits milk production efficiency in mammals

Efficient milk production in mammals confers evolutionary advantages by facilitating the transmission of energy from mother to offspring. However, the regulatory mechanism responsible for the gradual establishment of milk production efficiency in mammals, from marsupials to eutherians, remains elusive. Here, we find that mammary gland of the marsupial sugar glider contained milk components during adolescence, and that mammary gland development is less dynamically cyclic compared to that in placental mammals. Furthermore, fused in sarcoma (FUS) is found to be partially responsible for this establishment of low efficiency. In mouse model, FUS inhibit mammary epithelial cell differentiation through the cyclin-dependent kinase inhibitor p57Kip2, leading to lactation failure and pup starvation. Clinically, FUS levels are negatively correlated with milk production in lactating women. Overall, our results shed light on FUS as a negative regulator of milk production, providing a potential mechanism for the establishment of milk production from marsupial to eutherian mammals.

Haili Shao, Jipeng Huang, Hui Wang, Guolei Wang, Xu Yang, Mei Cheng, Changjie Sun, Li Zou, Qin Yang, Dandan Zhang, Zhen Liu, Xuelong Jiang, Lei Shi, Peng Shi, Baowei Han, Baowei Jiao