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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    ABSTRACT: The primitive endoderm epithelial structure in mouse blastocysts forms following cell differentiation and subsequent sorting, and this two-step process can be reproduced in vitro using an embryoid body model. We found that in the chimeric embryoid bodies consisting of paired wildtype and E-cadherin null ES cells, the wildtype sorted to the center and were enveloped by the less adhesive E-cadherin null cells, in accord with Steinberg's hypothesis. However, wildtype and N-cadherin null ES cells intermixed and did not segregate, a situation that may be explained by Albert Harris' modified principle, which incorporates the unique properties of living cells. Furthermore, in chimeric embryoid bodies composed of N-cadherin and E-cadherin null ES cells, the two weakly interacting cell types segregated but did not envelop one another. Lastly, the most consistent and striking observation was that differentiated cells sorted to the surface and formed an enveloping layer, regardless of the relative cell adhesive affinity of any cell combination, supporting the hypothesis that the ability of the differentiated cells to establish apical polarity is the determining factor in surface sorting and positioning.
    Biology Open 01/2014; 3(2). DOI:10.1242/bio.20146254 · 2.42 Impact Factor
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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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    ABSTRACT: Disabled-2 (Dab2) is an endocytic adaptor protein involved in clathrin-mediated endocytosis and cargo trafficking. Since its expression is lost in several cancer types, Dab2 has been suggested to be a tumor suppressor. In vitro studies indicate that Dab2 establishes epithelial cell polarity and organization by directing endocytic trafficking of membrane glycoproteins. Dab2 also modulates cellular signaling pathways by mediating the endocytosis and recycling of surface receptors and associated signaling components. Previously, two independent gene knockout studies have been reported, with some discrepancies in the observed embryonic phenotypes. To further clarify the in vivo roles of Dab2 in development and physiology, we designed a new floxed allele to delete dab2 gene. The constitutive dab2 deleted embryos showed a spectrum in the degree of endoderm disorganization in E5.5 and no mutant embryos persisted at E9.5. However, the mice were grossly normal when dab2 deletion was restricted to the embryo proper and the gene was retained in extraembryonic tissues using Meox2-Cre and Sox2-Cre. Adult Dab2-deficient mice had a small but statistically significant increase in serum cholesterol levels. The study of the new dab2 mutant allele in embryos and embryoid bodies confirms a role for Dab2 in extraembryonic endoderm development and epithelial organization. Experimental results with embryoid bodies suggest that additional endocytic adaptors such as Arh and Numb could partially compensate for Dab2 loss. Conditional deletion indicates that Dab2 is dispensable for organ development, when the vast majority of the embryonic cells are dab2 null. However, Dab2 has a physiological role in the endocytosis of lipoproteins and cholesterol metabolism.
    BMC Developmental Biology 10/2013; 13(1):39. DOI:10.1186/1471-213X-13-39 · 2.67 Impact Factor
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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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    ABSTRACT: The presence of an air‐filled organ (AO), either lungs or a swimbladder, is a defining character of the Osteichthyes (bony vertebrates, including tetrapods). Despite the functional and structural diversity of AOs, it was not previously known whether the same group of developmental regulatory genes are involved in the early development of both lungs and swimbladders. This study demonstrates that a suite of genes (Nkx2.1, FoxA2, Wnt7b, GATA6), previously reported to be co‐expressed only in the tetrapod lung, is also co‐expressed in the zebrafish swimbladder. We document the expression pattern of these genes in the adult and developing zebrafish swimbladder and compare the expression patterns to those in the mouse lung. Early‐acting genes involved in endoderm specification are expressed in the same relative location and stage of AO development in both taxa (FoxA2 and GATA6), but the order of onset and location of expression are not completely conserved for the later acting genes (Nkx2.1 and Wnt7b). Co‐expression of this suite of genes in both tetrapod lungs and swimbladders of ray‐finned fishes is more likely due to common ancestry than independent co‐option, because these genes are not known to be co‐expressed anywhere except in the AOs of Osteichthyes. Any conserved gene product interactions may comprise a character identity network (ChIN) for the osteichthyan AO.
    Evolution & Development 03/2013; 15(2). DOI:10.1111/ede.12022 · 2.72 Impact Factor
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