title: HOP/NECC1, a novel regulator of mouse trophoblast differentiation.
abstract: Homeodomain-only protein/not expressed in choriocarcinoma clone 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 placenta expressed HOP/NECC1 in the giant cell and spongiotrophoblast layers. HOP/NECC1 (-/-) placenta exhibited marked propagation of giant cell layers and, in turn reduction of spongiotrophoblast formation. We demonstrated SRF transcriptional activity increased in the differentiating trophoblasts and forced expression of SRF in a trophoblast stem (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 cell lineage and result in non-lethal defects shown by the HOP/NECC1 (-/-) placentas.
authors.affiliation: Division of Molecular and Cell Therapeutics, Kyushu University, Japan. asanoma@med.kyushu-u.ac.jp
authors.forename: Kazuo
authors.initials: K
authors.lastname: Asanoma
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kato
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Chong Hyun
authors.initials: CH
authors.lastname: Shin
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyanari
authors.forename: Koji
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Kenzo
authors.initials: K
authors.lastname: Sonoda
authors.forename: Kotaro
authors.initials: K
authors.lastname: Fukushima
authors.forename: Norio
authors.initials: N
authors.lastname: Wake
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D005260:Female; D020869:Gene Expression Profiling; D005838:Genotype; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D013997:Time Factors; D014327:Trophoblasts / Q000166:cytology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C476884:HOPX protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins