During mouse embryo development, Pax7+/Myf5+ progenitor cells give rise to both muscle progenitor cells (MPC) and brown adipocytes (BA). The E2F4/p107/p130 axis was found to repress the expression of Prdm16 – a lineage-determination factor of BA – in these progenitor cells to suppress their brown adipogenic fate in culture. Similarly, knockdown of E2f4 in preadipocytes (CD31-/CD45-/Sca1+) collected from white adipose tissue (WAT) of adult mice was also found to upregulate PRDM16 and UCP1 expression in newly formed mature adipocytes in culture, suggesting E2F4 may play a role in white fat browning as well. However, it remains unclear whether E2F4 indeed regulates brown adipose tissue (BAT) development or white fat browning in vivo or not. We generated several E2F4-null mouse mod...[ Read more ]

During mouse embryo development, Pax7+/Myf5+ progenitor cells give rise to both muscle progenitor cells (MPC) and brown adipocytes (BA). The E2F4/p107/p130 axis was found to repress the expression of Prdm16 – a lineage-determination factor of BA – in these progenitor cells to suppress their brown adipogenic fate in culture. Similarly, knockdown of E2f4 in preadipocytes (CD31-/CD45-/Sca1+) collected from white adipose tissue (WAT) of adult mice was also found to upregulate PRDM16 and UCP1 expression in newly formed mature adipocytes in culture, suggesting E2F4 may play a role in white fat browning as well. However, it remains unclear whether E2F4 indeed regulates brown adipose tissue (BAT) development or white fat browning in vivo or not. We generated several E2F4-null mouse models to test the hypothesis. We found that deletion of E2f4 in Pax7+/Myf5+ embryonic progenitor cells of BAT in developing embryos was insufficient to promote brown adipogenesis during development. Nor was the ablation of E2F4 in differentiated adipocytes in WAT sufficient to promote white fat browning. In addition, Paxbp1, a binding partner of Pax7 in MPC, was also examined in vivo for its role in brown and beige fat formation. We found that ablation of Paxbp1 compromised formation of both brown and beige fat in vivo.