Visceral Endoderm Expression of Yin-Yang1 (YY1) Is Required for VEGFA Maintenance and Yolk Sac Development

Rhee, Siyeon; Guerrero-Zayas, Mara-Isel; Wallingford, Mary C.; Ortíz-Pineda, Pablo A.; Mager, Jesse; Tremblay, Kimberly D.

doi:10.1371/journal.pone.0058828

Cited by 20 publications

(13 citation statements)

References 50 publications

(69 reference statements)

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“…Immunofluorescence was performed as previously published [15], but treated with a serum block as opposed to a milk block. Heat mediated antigen retrieval was performed with 0.01 M Tris Base pH10.0.…”

Section: Methodsmentioning

confidence: 99%

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

Wallingford

Gammill

Giachelli

2016

Reproductive Biology

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The essential nutrient phosphorus must be taken up by the mammalian embryo during gestation. The mechanism(s) and key proteins responsible for maternal to fetal phosphate transport have not been identified. Established parameters for placental phosphate transport match those of the type III phosphate transporters, Slc20a1 and Slc20a2. Both members are expressed in human placenta, and their altered expression is linked to preeclampsia. In this study, we tested the hypothesis that Slc20a2 is required for placental function. Indeed, complete deficiency of Slc20a2 in either the maternal or embryonic placental compartment results in fetal growth restriction. We found that Slc20a2 null mice can reproduce, but are subviable; ~50% are lost prior to weaning age. We also observed that 23% of Slc20a2 deficient females develop pregnancy complications at full term, with tremors and placental abnormalities including abnormal vascular structure, increased basement membrane deposition, abundant calcification, and accumulation of novel CD13 and lamininα1 positive cells. Together these data support that Slc20a2 deficiency impacts both maternal and neonatal health, and Slc20a2 is required for normal placental function. In humans, decreased levels of placental Slc20a1 and Slc20a2 have been correlated with early onset preeclampsia, a disorder that can manifest from placental dysfunction. In addition, preterm placental calcification has been associated with poor pregnancy outcomes. We surveyed placental calcification in human preeclamptic placenta samples, and detected basement membrane-associated placental calcification as well as a comparable lamininα1 positive cell type, indicating that similar mechanisms may underlie both human and mouse placental calcification.

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Section: Methodsmentioning

confidence: 99%

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

Wallingford

Gammill

Giachelli

2016

Reproductive Biology

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“…The yolk sac layers were separated using the trypsin/pancreatin method as described in (Rhee et al, 2013). Briefly, yolk sacs were collected and incubated in Tyrode Ringers Solution (Fisher S25512) containing 0.005g/mL Trypsin (Fisher S25618) and 0.025g/mL Pancreatin (Fisher S25456) for 4h at 4°C with gentle shaking.…”

Section: Methodsmentioning

confidence: 99%

Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm

Wallingford

Giachelli

2014

Mechanisms of Development

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PiT-1 protein is a transmembrane sodium-dependent phosphate (Pi) transporter. PiT-1 knock out (KO) embryos die from largely unknown causes by embryonic day (E) 12.5. We tested the hypothesis that PiT-1 is required for endocytosis in the embryonic yolk sac (YS) visceral endoderm (VE). Here we present data supporting that PiT-1 KO results in a YS remodeling defect and decreased endocytosis in the YS VE. The remodeling defect is not due to an upstream cardiomyocyte requirement for PiT-1, as SM22αCre-specific KO of PiT-1 in the developing heart and the YS mesodermal layer (ME) does not recapitulate the PiT-1 global KO phenotype. Furthermore, we find that high levels of PiT-1 protein localize to the YS VE apical membrane. Together these data support that PiT-1 is likely required in YS VE. During normal development maternal immunoglobulin (IgG) is endocytosed into YS VE and accumulates in the apical side of the VE in a specialized lysosome termed the apical vacuole (AV). We have identified a reduction in PiT-1 KO VE cell height and a striking loss of IgG accumulation in the PiT-1 KO VE. The endocytosis genes Tfeb, Lamtor2 and Snx2 are increased at the RNA level. Lysotracker Red staining reveals a loss of distinct AVs, and yolk sacs incubated ex vivo with phRODO Green Dextran for Endocytosis demonstrate a functional loss of endocytosis. As yolk sac endocytosis is controlled in part by microautophagy, but expression of LC3 had not been examined, we investigated LC3 expression during yolk sac development and found stage-specific LC3 RNA expression that is predominantly from the YS VE layer at E9.5. Normalized LC3-II protein levels are decreased in the PiT-1 KO YS, supporting a requirement for PiT-1 in autophagy in the YS. Therefore, we propose the novel idea that PiT-1 is central to the regulation of endocytosis and autophagy in the YS VE.

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“…YS endodermal cells are an absorptive epithelial cell type which actively transports nutrients to the mesenchymal layer of the YS. Trafficking takes place via the formation of lysosomes which can be fluorescently labelled (Rhee et al, 2013). Gastrokine-2 is secreted by the gastric epithelial cells at the tips of the antrum villi into the gastric juices.…”

Section: Gastrokine-2 Protein Expression In the Ysmentioning

confidence: 99%

Gastrokine-2 is transiently expressed in the endodermal and endothelial cells of the maturing mouse yolk sac

Antas¹,

Brigden²,

Prudence³

et al. 2014

Gene Expression Patterns

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Visceral Endoderm Expression of Yin-Yang1 (YY1) Is Required for VEGFA Maintenance and Yolk Sac Development

Cited by 20 publications

References 50 publications

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

Slc20a2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells

Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm

Gastrokine-2 is transiently expressed in the endodermal and endothelial cells of the maturing mouse yolk sac

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