Fig. 8

Proposed model of regulation of trophoblast stem cell proliferation and endoreduplication by Hippo. In TSCs, a substantial pool of YAP remains unphosphorylated and translocate to the nucleus. Nuclear YAP sequesters CDX2, thereby controlling trophoblast proliferation by reducing CYCLIN D1 levels. LATS1 in TSCs form LATS1-LIMK2 complex resulting in reduced activation of LIMK2 followed by reduced COFILIN inactivation. On the other hand, phosphorylation of YAP at ser127 prevents it from translocating into the nucleus when TSCs are induced to differentiate. Here, scarcity of LATS1 activates LIMK2 by enhancing pLIMK2Thr⁵⁰⁵ which phosphorylate COFILIN and inhibit it from depolymerizing actin. As a result, endoreduplicated trophoblast giant cell formation occurs