title: Loss of heterochromatin protein 1 gamma reduces the number of primordial germ cells via impaired cell cycle progression in mice.
abstract: Signals from extraembryonic tissues in mice determine which proximal epiblast cells become primordial germ cells (PGCs). After their specification, approximately 40 PGCs appear at the base of the allantoic bud and migrate to the genital ridges, where they expand to about 25 000 cells by Embryonic Day (E)13.5. The heterochromatin protein 1 (HP1) family members HP1alpha, HP1beta, and HP1gamma (CBX5, CBX1, and CBX3, respectively) are thought to induce heterochromatin structure and to regulate gene expression by binding methylated histone H3 lysine 9. We found a dramatic loss of germ cells before meiosis in HP1gamma mutant (HP1gamma(-/-)) mice that we generated previously. The reduction in PGCs in HP1gamma(-/-) embryos was detectable from the early bud stage (E7.25), and the number of HP1gamma(-/-) PGCs was gradually reduced thereafter. Bromodeoxyuridine incorporation into PGCs was significantly reduced in E7.25 and E12.5 HP1gamma(-/-) embryos. Furthermore, a lower proportion of HP1gamma(-/-) PGCs than wild-type PGCs was in S phase, and a higher proportion, respectively, was in G1 phase at E12.5. Moreover, the proportion of p21 (Cip, official symbol CDKN1A)-positive HP1gamma(-/-) PGCs was increased, suggesting that the G1/S phase transition was inhibited. However, no differences were detected between fate determination, migration, apoptosis, or histone modification of PGCs of control embryos and those of HP1gamma(-/-) embryos. Therefore, the reduction in PGCs in HP1gamma(-/-) embryos could be caused by impaired cell cycle in PGCs. These results suggest that HP1gamma plays an important role in keeping enough germ cells by regulating the PGC cell cycle.
authors.affiliation: Divisions of Transgenic Animal Science and Functional Genomics, Advanced Science Research Center, Kanazawa University, Kanazawa, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Abe
authors.forename: Chie
authors.initials: C
authors.lastname: Naruse
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kato
authors.forename: Takumi
authors.initials: T
authors.lastname: Nishiuchi
authors.forename: Mitinori
authors.initials: M
authors.lastname: Saitou
authors.forename: Masahide
authors.initials: M
authors.lastname: Asano
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005854:Germ Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal
chemical_list: C453799:Cbx3 protein, mouse; D002868:Chromosomal Proteins, Non-Histone