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. It encodes a protein with a SAP-like domain 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, 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 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. These findings suggest a similar role for STELLA during early human development as in mice and a potential involvement in germ cell tumors.

Primordial Germ Cells in Mice

“…It has thus been proposed that the Stella-positive and Hox-negative cells are the established PGCs (Saitou et al 2002). Gene-knockout studies, however, revealed that neither Fragilis nor Stella is essential for PGC specification (Payer et al 2003;Lange et al 2008). Instead, Stella has been found to be a critical factor to protect the maternal genome and paternally imprinted genes from genome-wide DNA demethylation that occurs in the zygotes (Nakamura et al 2007), whereas Fragilis has a critical function in restricting the replication of multiple pathogenic viruses including influenza (Brass et al 2009;Everitt et al 2012).…”

Diverse Epigenetic Profile of Novel Human Embryonic Stem Cell Lines

“…10 Some of these genes were later considered as embryonic stem cell-specific genes. [11][12][13]16 We decided to study changes of the expression level of particular OCT4-related genes that were reactivated in cloned mouse blastocysts during hESCs differentiation. 10 Human orthologues of mouse DPPA3 and DPPA5 were chosen.…”

“…It is important to mention that human NANOG and DPPA3 are located on the same chromosome 12, in close proximity. 13,14 Thus, differential methylation of the adjacent regions in vitro in ES cell culture indicates the inheritance of highly coordinated epigenetic regulation during early embryonic development. Another explanation may come from the genetic background of the cell lines.…”

“…5,8,9 OCT4-related genes, particularly DPPA3 and DPPA5, have been proposed to contribute to early embryogenesis and may be specific markers of ES cells. [10][11][12][13][14] Their expression was detected in pluripotent cells and tissues and no expression was found in normal somatic tissues. 10 Recent studies indicate that independently derived hESC lines have similar gene expression profile.…”

Fully-mature antral mouse oocytes are transcriptionally silent but their heterochromatin maintains a transcriptional permissive histone acetylation profile

“…When the expression of one of the 27 maternal-effect factors identified so far is altered, mouse embryos arrest development, mostly at the 2-cell stage (for a review see [13]). We have recently shown that one of the possible causes of the developmental incompetence of MII NSN oocytes is the down-regulation of two maternaleffect factors, OCT4 and STELLA [27,28], required for development beyond the 2-cell stage [8,20].…”