Dynamic GATA6 Expression in Primitive Endoderm Formation and Maturation in Early Mouse Embryogenesis

Ovarian Cancer Programs, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Developmental Dynamics (Impact Factor: 2.38). 10/2008; 237(10):2820-9. DOI: 10.1002/dvdy.21703
Source: PubMed


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.

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    • "In early mammalian embryos following implantation of the blastocysts, the inner cell mass expands, and induction of GATA6 determines differentiation into primitive endoderm (Cai et al., 2008), which subsequently forms visceral and parietal endoderm. Within the inner cell mass, cells actively sort and position to form a primitive endoderm layer covering the surface (Rossant et al., 2003; Chazaud et al., 2006; Plusa et al., 2008; Meilhac et al., 2009; Morris et al., 2010; Frankenberg et al., 2011), and cell adhesion molecules including E-cadherin and N-cadherin mediate the cell–cell interactions (Gumbiner, 1996; Gumbiner, 2005; Moore et al., 2009). "
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    • "Primary antibodies used in this study were: mouse monoclonal anti-Dab2 (BD Transduction Laboratories); rabbit polyclonal anti-Dab2 [18]; rabbit polyclonal anti-Gata4 antibodies (Santa Cruz Biotechnology, Inc.); rabbit pan anti-laminin (Abcam); rabbit polyclonal anti-GATA6 [70]; mouse monoclonal anti-Oct3/4 (Santa Cruz Biotechnology); mouse monoclonal anti-Arh (Santa Cruz Biotechnology, Inc.); goat polyclonal anti-Numb (Abcam), and mouse monoclonal anti-beta-actin (BD Transduction Laboratories). DAPI (4′-6-diamidino-2-phenylindole) was used as a generic nuclear counterstain and applied at the terminal stages of the procedure. "
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    • "Expression of both Nkx2.1a and Nkx2.1b in the swimbladder is likely due to the expression of an Nkx2.1 homolog in the AO of the common ancestor of mouse and zebrafish and subsequent duplication of Nkx2.1 during the whole genome duplication that Fig. 7. Timing of expression of candidate genes in mouse (A) and zebrafish (B). FoxA2 and GATA6 expression times are both expressed from early specification of the AO domain through adult in both mouse and zebrafish but divergent during very early development; they are expressed from early endoderm specification [FoxA2 from E5.5 (Perea‐Gomez et al. 1999); FoxA2 from 8 hpf (Cheng et al. 2008); mouse GATA6 from E4.5 (Cai et al. 2008); zebrafish GATA6 (Zeng et al. 2009)] through adult (mouse FoxA2: Zhou et al. 1996; FoxA2: Field et al. 2003; mouse GATA6: Morrisey et al. 1998; zebrafish GATA6: Yee et al. 2005). Nkx2.1 and Wnt7b expression differs during our period of interest. "
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