Title: stella Is a Maternal Effect Gene Required for Normal Early Development in Mice
Abstract: stella is a novel gene specifically expressed in primordial germ cells, oocytes, preimplantation embryos, and pluripotent cells [1Sato M. Kimura T. Kurokawa K. Fujita Y. Abe K. Masuhara M. Yasunaga T. Ryo A. Yamamoto M. Nakano T. Identification of PGC7, a new gene expressed specifically in preimplantation embryos and germ cells.Mech. Dev. 2002; 113: 91-94Crossref Scopus (198) Google Scholar, 2Saitou M. Barton S.C. Surani M.A. A molecular programme for the specification of germ cell fate in mice.Nature. 2002; 418: 293-300Crossref PubMed Scopus (679) Google Scholar]. It encodes a protein with a SAP-like domain [3Aravind L. Koonin E.V. SAP––a putative DNA-binding motif involved in chromosomal organization.Trends Biochem. Sci. 2000; 25: 112-114Abstract Full Text Full Text PDF PubMed Scopus (394) Google Scholar] and a splicing factor motif-like structure, suggesting possible roles in chromosomal organization or RNA processing. Here, we have investigated the effects of a targeted mutation of stella in mice. We show that while matings between heterozygous animals resulted in the birth of apparently normal stella null offspring, stella-deficient females displayed severely reduced fertility due to a lack of maternally inherited Stella-protein in their oocytes. Indeed, we demonstrate that embryos without Stella are compromised in preimplantation development and rarely reach the blastocyst stage. stella is thus one of few known mammalian maternal effect genes [4Wu X. Viveiros M.M. Eppig J.J. Bai Y. Fitzpatrick S.L. Matzuk M.M. Zygote arrest 1 (Zar1) is a novel maternal-effect gene critical for the oocyte-to-embryo transition.Nat. Genet. 2003; 33: 187-191Crossref PubMed Scopus (324) Google Scholar, 5Tong Z.B. Gold L. Pfeifer K.E. Dorward H. Lee E. Bondy C.A. Dean J. Nelson L.M. Mater, a maternal effect gene required for early embryonic development in mice.Nat. Genet. 2000; 26: 267-268Crossref PubMed Scopus (398) Google Scholar, 6Howell C.Y. Bestor T.H. Ding F. Latham K.E. Mertineit C. Trasler J.M. Chaillet J.R. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene.Cell. 2001; 104: 829-838Abstract Full Text Full Text PDF PubMed Scopus (542) Google Scholar, 7Christians E. Davis A.A. Thomas S.D. Benjamin I.J. Maternal effect of Hsf1 on reproductive success.Nature. 2000; 407: 693-694Crossref PubMed Scopus (222) Google Scholar, 8Gurtu V.E. Verma S. Grossmann A.H. Liskay R.M. Skarnes W.C. Baker S.M. Maternal effect for DNA mismatch repair in the mouse.Genetics. 2002; 160: 271-277Google Scholar, 9Burns K.H. Viveiros M.M. Ren Y. Wang P. DeMayo F.J. Frail D.E. Eppig J.J. Matzuk M.M. Roles of NPM2 in chromatin and nucleolar organization in oocytes and embryos.Science. 2003; 300: 633-636Crossref PubMed Scopus (283) Google Scholar], as the phenotypic effect on embryonic development is mainly a consequence of the maternal stella mutant genotype. Furthermore, we show that STELLA that is expressed in human oocytes [10Goto T. Jones G.M. Lolatgis N. Pera M.F. Trounson A.O. Monk M. Identification and characterisation of known and novel transcripts expressed during the final stages of human oocyte maturation.Mol. Reprod. Dev. 2002; 62: 13-28Crossref PubMed Scopus (36) Google Scholar] is also expressed in human pluripotent cells and in germ cell tumors. Interestingly, human chromosome 12p, which harbours STELLA, is consistently overrepresented in these tumors [11Looijenga L.H. Zafarana G. Grygalewicz B. Summersgill B. Debiec-Rychter M. Veltman J. Schoenmakers E.F. Rodriguez S. Jafer O. Clark J. et al.Role of gain of 12p in germ cell tumour development.APMIS. 2003; 111 (discussion 172–173): 161-171Crossref PubMed Scopus (111) Google Scholar]. These findings suggest a similar role for STELLA during early human development as in mice and a potential involvement in germ cell tumors.