The Study Of The Roles Of Wntless In Hair Follicle Development,Hair Cycling And Epidermal Homeostasis And The Function Of Foxp1 In Brown Adipose Tissue Formation And Function

Wnt signaling plays essential roles in the development and homeostasis of skin and related appendages in mice. In recent years, Wls has been identified as an important component of Wnt pathway, and acts as a transportor of Wnt ligands to facilitate their secretion from Wnt producing cells. Although considerable attention has been paid on the function of Wls in mammal development and human diseases, the precise roles of Wls in these processes are far from clear. In this research, we used epidermal specific K14-cre to knockout Wls in mice. With this model, we systematically studied the function of Wls in hair follicle development, hair cycle and postnatal epidermal homeostasis. We found the initiation of hair follicle development in K14-cre;Wlsc/c knockout mice is interrupted, characterized by reduced placode number. As a result, the amount of hair follicle decreases. The postnatal hair cycle is also affected upon Wls deletion, and Wls-deficient hair follicles precociously regress and fail to re-enter into the new anagen phase. At molecular level, Wls deletion results in the impaired activity of β-catenin-dependent canonical Wnt signal pathway. By comparing the phenotypes of K14-cre;Wlsc/c and K14-cre;β-cateninc/c mice, we found high similarity of defects between these two mutants. These data suggest Wls regulates hair follicle development and epidermal homeostasis through mediating Wnt/?-catenin pathway.Meanwhile, we explored the role of transcription factor Foxp1 in regulating the formation and fucntion of brown adipose tissue. Fox superfamily is composed of multiple members, which participate in mediating the development and homeostasis of various organs and tissues. As a member of Fox family, Foxp1 has been reported to play pivotal roles in controlling nervous system development, hair cycling and immune-regulation, etc. Previous reports have identified some Fox proteins are involved in regulating the formation and function of adipose tissue. However, the function of Foxp1 in adipose tissue formation and metabolism remains unclear. Through cellular assays and phenotypic analysis of Foxp1 conditioned knockout mouse model, we found Foxp1 is an important regulator in repressing the formation and function of brown adipose tissue. Deleting Foxp1 with adipocyte-specific AP2-cre results in expanded brown adipose tissue and elevated oxygen comsumption whereas energe-storing white adipose tissue volume reduces correspondingly. Molecularly, Foxp1 is able to directly bind to the promoter regions of brown adipose tissue-related genes to regulate their transcription. Foxp1 can also bind to PRDM16 and antagonize its function, thus inhibits the formation and function of brown adipose tissue.