HOP/NECC1, A Novel Regulator of Mouse Trophoblast Differentiation

Abstract Homeodomain-only protein/not expressed in choriocarcinomaclone 1 (HOP/NECC1) is a newly identified gene that modifies the expression of cardiac-specific genes and thereby regulates heart development. More recently, HOP/NECC1 was reported to be a suppressor of choriocarcinogenesis. Here, we examined the temporal expression profile of HOP/NECC1 in wild-type mouse placenta. We found that E8.5–E9.5 wild-type placentaexpressed HOP/NECC1 in the giant celland spongiotrophoblast layers. HOP/NECC1 (-/-) placentaexhibited marked propagation of giant celllayers and, in turn reduction of spongiotrophoblast formation. We demonstrated SRF transcriptional activity increased in the differentiating trophoblastsand forced expression of SRF in a trophoblaststem (TS) cell line induces the differentiation into giant cells. Negative regulation of SRF ( serum response factor) by the binding of HOP/NECC1 protein contributed at least in part to the generation of these placental defects. Gradual induction of HOP/NECC1 in response to differentiation stimuli may result in the decision to differentiate into a particular type of trophoblastic celllineage and result in non-lethal defects shown by the HOP/NECC1 (-/-) placentas.