Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition.
The female gamete (the oocyte) serves the distinct purpose of transmitting the maternal genome and other maternal factors that are critical for post-ovulation events. Through the identification and characterization of oocyte-specific factors, we are beginning to appreciate the diverse functions of oocytes in ovarian folliculogenesis, fertilization and embryogenesis. To understand these processes further, we identified genes called zygote arrest 1 (Zar1 and ZAR1 in mouse and human, respectively) as novel oocyte-specific genes. These encode proteins of 361 amino acids and 424 amino acids, respectively, which share 59% amino-acid identity and an atypical plant homeo-domain (PHD) motif. Although Zar1-null (Zar1(-/-)) mice are viable and grossly normal, Zar1(-/-) females are infertile. Ovarian development and oogenesis through the early stages of fertilization are evidently unimpaired, but most embryos from Zar1(-/-) females arrest at the one-cell stage. Distinct pronuclei form and DNA replication initiates, but the maternal and paternal genomes remain separate in arrested zygotes. Fewer than 20% of the embryos derived from Zar1(-/-) females progress to the two-cell stage and show marked reduction in the synthesis of the transcription-requiring complex, and no embryos develop to the four-cell stage. Thus, Zar1 is the first identified oocyte-specific maternal-effect gene that functions at the oocyte-to-embryo transition and, as such, offers new insights into the initiation of embryonic development and fertility control in mammals.
Wu
Xuemei
X
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Viveiros
Maria M
MM
Eppig
John J
JJ
Bai
Yuchen
Y
Fitzpatrick
Susan L
SL
Matzuk
Martin M
MM
D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D003001:Cloning, Molecular; D004261:DNA Replication; D004527:Egg Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology; D005307:Fertilization in Vitro; D005786:Gene Expression Regulation; D015723:Gene Library; D006041:Goats; D066298:In Vitro Techniques; D008297:Male; D008540:Meiosis; D051379:Mice / Q000196:embryology*; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009865:Oocytes / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013087:Spermatids / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology; D015053:Zygote / Q000378:metabolism*
D004527:Egg Proteins; D012333:RNA, Messenger; C471631:Zar1 protein, human; C471630:Zar1 protein, mouse