Dynamic GATA6 expression in primitive endoderm formation and maturation in early mouse embryogenesis

Abstract

The derivation of the primitive endoderm layer from the pluripotent cells of the inner cell mass is one of the earliest differentiation and morphogenic events in embryonic development. GATA4 and GATA6 are the key transcription factors in the formation of extraembryonic endoderms, but their specific contribution to the derivation of each endoderm lineage needs clarification. We further analyzed the dynamic expression and mutant phenotypes of GATA6 in early mouse embryos. GATA6 and GATA4 are both expressed in primitive endoderm cells initially. At embryonic day (E) 5.0, parietal endoderm cells continue to express both GATA4 and GATA6; however, visceral endoderm cells express GATA4 but exhibit a reduced expression of GATA6. By and after E5.5, visceral endoderm cells no longer express GATA6. We also found that GATA6 null embryos did not form a morphologically recognizable primitive endoderm layer, and subsequently failed to form visceral and parietal endoderms. Thus, the current study establishes that GATA6 is essential for the formation of primitive endoderm, at a much earlier stage then previously recognized, and expression of GATA6 discriminates parietal endoderm from visceral endoderm lineages. Developmental Dynamics 237: 2820 -2829, 2008.

Ectopic expression of Fgf3 leads to aberrant lineage segregation in the mouse parthenote preimplantation embryos

“…S4A, B), we assessed other Fgf ligands to identify which one may cause the increased phosphorylation of Fgfr2 in parthenotes. It was shown that Fgf3 and Gata4/6 were co-expressed in the parietal endoderm of post-implantation embryos (Shimosato et al, 2007;Cai et al, 2008;Pilon et al, 2008). Hence we analyzed Fgf3 immunostaining and found that, in contrast to control embryos, which revealed only background levels of Fgf3, parthenotes showed strong Fgf3-positive signals throughout all plasma membranes of both morulae and blastocysts (Fig.…”

“…All of the aforementioned genes are pivotal factors regulating lineage segregation and cell fate determination (Russ et al, 2000;Strumpf et al, 2005;Shimosato et al, 2007;Cai et al, 2008). Similar to Tbr2(Eomes) homozygous mutants, most parthenote embryos demonstrated a lack of diploid dividing trophoblast cells, impaired or retarded development of the neuroectoderm and brain, and multiple mesodermal defects (Sturm et al, 1994;Bulfone et al, 1999;Russ et al, 2000;Kwon and Hadjantonakis, 2007).…”

“…Impaired proliferation and differentiation were observed in both extraembryonic and embryonic lineages of parthenote embryos, especially in the extraembryonic and embryonic mesoderm as well as primitive endoderm lineages (Barton et al, 1985;Sturm et al, 1994;Mognetti and Sakkas, 1996). Gata4 and Gata6 are two essential marker genes of the primitive endoderm (Boyer et al, 2006;Yamanaka et al, 2006;Cai et al, 2008;Kuijk et al, 2008), which forms yolk sac and is a major affected lineage in parthenote embryos (Sturm et al, 1994;Newman-Smith and Werb, 1995;Chazaud et al, 2006;Yamanaka et al, 2006). Our observation of the overexpression of the parietal endoderm marker genes, Gata4 and Fgf3, in parthenote ICMs is consistent with the previously reported tendency of parthenote ICM outgrowths to differentiate into parietal endoderm cells, which are descendants of the primitive endoderm (Newman-Smith and Werb, 1995;Boyer et al, 2006;Cai et al, 2008).…”

“…Gata4 and Gata6 are two essential marker genes of the primitive endoderm (Boyer et al, 2006;Yamanaka et al, 2006;Cai et al, 2008;Kuijk et al, 2008), which forms yolk sac and is a major affected lineage in parthenote embryos (Sturm et al, 1994;Newman-Smith and Werb, 1995;Chazaud et al, 2006;Yamanaka et al, 2006). Our observation of the overexpression of the parietal endoderm marker genes, Gata4 and Fgf3, in parthenote ICMs is consistent with the previously reported tendency of parthenote ICM outgrowths to differentiate into parietal endoderm cells, which are descendants of the primitive endoderm (Newman-Smith and Werb, 1995;Boyer et al, 2006;Cai et al, 2008). Interestingly, we detected Gata4 expression as early as the morula stage, while previous studies failed to detect Gata4 expression till the midblastocyst stage (Plusa et al, 2008;Silva et al, 2009;Yamanaka et al, 2010).…”

Spécification de l’épiblaste et de l’endoderme primitif lors du développement embryonnaire préimplantatoire chez la souris

“…L'invalidation génique de Gata6 entraîne, quant à elle, une absence d'épithélium d'EPr à E4,5 indiquant que Gata6 est requis pour sa mise en place [9]. Néanmoins, ces analyses, pour être plus précises, nécessitaient une étude des phénotypes aux stades plus précoces, avant 4,5 jours après la fécon-dation.…”