ORCID Profile
0000-0001-8365-455X
Current Organisation
Queen's University
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Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1111/J.1432-0436.2006.00103.X
Abstract: The placenta forms a complex interface between the mother and fetus during development that is designed for efficient nutrient exchange. A large surface area is created by extensive branching morphogenesis of the trophoblast-derived epithelium to create a villous network, called the labyrinth in rodents. These villi are subsequently vascularized with an elaborate capillary network. Morphogenesis begins with selection of a subset of trophoblast cells in the basal layer of the chorion that express the Gcm1 transcription factor. These cells leave the cell cycle and undergo cell shape changes that initiate a process of involution to create primary villi into which fetal blood vessels grow. Much less is known about the regulation of subsequent events in branching, certainly compared with other organs. However, over 60 different mouse mutants have defects during later labyrinth development. Some of these mutant genes encode components of signaling pathways such as the fibroblast growth factor and Wnt pathways that play evolutionarily conserved roles in other branched organs, These mutants represent a still largely untapped resource as most of them have not been studied in detail in relation to placental morphogenesis.
Publisher: Elsevier BV
Date: 03-2015
DOI: 10.1016/J.PLACENTA.2014.12.002
Abstract: Retinoic acid (RA) signaling is a well known regulator of trophoblast differentiation and placental development, and maternal decidual cells are recognized as the source of much of this RA. We explored possible trophoblast-derived sources of RA by examining the expression of RA synthesis enzymes in the developing mouse placenta, as well as addressed potential sites of RA action by examining the ontogeny of gene expression for other RA metabolizing and receptor genes. Furthermore, we investigated the effects of endogenous RA production on trophoblast differentiation. Placental tissues were examined by in situ hybridization and assayed for RARE-LacZ transgene activity to locate sites of RAR signaling. Trophoblast stem cell cultures were differentiated in the presence of ALDH1 inhibitors (DEAB and citral), and expression of labyrinth (Syna, Ctsq) and junctional zone (Tpbpa, Prl7b1, Prl7a2) marker genes were analyzed by qRT-PCR. We show Aldh1a3 is strongly expressed in a subset of ectoplacental cone cells and in glycogen trophoblast cells of the definitive murine placenta. Most trophoblast subtypes of the placenta express RA receptor combinations that would enable them to respond to RA signaling. Furthermore, expression of junctional zone markers decrease in differentiating trophoblast cultures when endogenous ALDH1 enzymes are inhibited. Aldh1a3 is a novel marker for glycogen trophoblast cells and their precursors and may play a role in the differentiation of junctional zone cell types via production of a local source of RA.
Publisher: Elsevier BV
Date: 03-2008
DOI: 10.1016/J.PLACENTA.2007.11.006
Abstract: Stem cells that can be derived from fetal membranes represent an exciting field of research that bears tremendous potential for developmental biology and regenerative medicine. In this report we summarize contributions to a workshop in which newest insights into the characteristics, subtypes and molecular determinants of stem cells from trophoblast and endometrial tissues were presented.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.PLACENTA.2013.05.011
Abstract: In the present study, we characterized the expression of lymphocyte antigen 6, locus E (Ly6e) in mouse placental trophoblast. We identified Ly6e mRNA expression in trophoblast stem (TS) cells by a gene expression screen. In vivo, Ly6e was first detectable by mRNA in situ hybridization in the chorion beginning at E8.5 with spatial expression similar to Syncytin a (Syna). At later stages of gestation, Ly6e was restricted to syncytiotrophoblast in the labyrinth. Northern blot confirmed that Ly6e was expressed in both undifferentiated and differentiated TS cell cultures but that its expression increased with differentiation. FACS analysis confirmed these results and allowed us to isolate LY6E⁺ cells, which we found to express Syna at a much higher level than did LY6E⁻ cells. Our findings suggest that LY6E is expressed in differentiated syncytiotrophoblast and may also be useful as an early marker, expressed in progenitors of this cell-type.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.PLACENTA.2009.12.008
Abstract: Workshops are an important part of the annual meeting of the International Federation of Placenta Associations (IFPA). At IFPA Meeting 2009 erse topics were discussed in twelve themed workshops. Topics covered included: immune response to pregnancy signaling between fetus and placenta bioactive lipids in placenta placenta in agricultural species epigenetics and placentation trophoblast deportation glucocorticoids and placental function endothelium placental transport genes and placenta uteroplacental blood flow and placental stem cells. This report is a full summary of the various topics covered.
Publisher: Springer Science and Business Media LLC
Date: 02-03-2018
DOI: 10.1038/S41598-018-22040-2
Abstract: Fetal growth and survival is dependent on the elaboration and propinquity of the fetal and maternal circulations within the placenta. Central to this is the formation of the interhaemal membrane, a multi-cellular lamina facilitating exchange of oxygen, nutrients and metabolic waste products between the mother and fetus. In rodents, this cellular barrier contains two transporting layers of syncytiotrophoblast, which are multinucleated cells that form by cell-cell fusion. Previously, we reported the expression of the GPI-linked cell surface protein LY6E by the syncytial layer closest to the maternal sinusoids of the mouse placenta (syncytiotrophoblast layer I). LY6E has since been shown to be a putative receptor for the fusogenic protein responsible for fusion of syncytiotrophoblast layer I, Syncytin A. In this report, we demonstrate that LY6E is essential for the normal fusion of syncytiotrophoblast layer I, and for the proper morphogenesis of both fetal and maternal vasculatures within the placenta. Furthermore, specific inactivation of Ly6e in the epiblast, but not in placenta, is compatible with embryonic development, indicating the embryonic lethality reported for Ly6e −/− embryos is most likely placental in origin.
Publisher: The Company of Biologists
Date: 15-06-2008
DOI: 10.1242/DEV.020099
Abstract: The labyrinth of the rodent placenta contains villi that are the site of nutrient exchange between mother and fetus. They are covered by three trophoblast cell types that separate the maternal blood sinusoids from fetal capillaries - a single mononuclear cell that is a subtype of trophoblast giant cell (sinusoidal or S-TGC) with endocrine function and two multinucleated syncytiotrophoblast layers, each resulting from cell-cell fusion, that function in nutrient transport. The developmental origins of these cell types have not previously been elucidated. We report here the discovery of cell-layer-restricted genes in the mid-gestation labyrinth (E12.5-14.5)including Ctsq in S-TGCs (also Hand1-positive), Syna in syncytiotrophoblast layer I (SynT-I), and Gcm1,Cebpa and Synb in syncytiotrophoblast layer II (SynT-II). These genes were also expressed in distinct layers in the chorion as early as E8.5,prior to villous formation. Specifically, Hand1 was expressed in apical cells lining maternal blood spaces (Ctsq is not expressed until E12.5), Syna in a layer immediately below, and Gcm1,Cebpa and Synb in basal cells in contact with the allantois. Cebpa and Synb were co-expressed with Gcm1 and were reduced in Gcm1 mutants. By contrast, Hand1 and Syna expression was unaltered in Gcm1 mutants, suggesting that Gcm1-positive cells are not required for the induction of the other chorion layers. These data indicate that the three differentiated trophoblast cell types in the labyrinth arise from distinct and autonomous precursors in the chorion that are patterned before morphogenesis begins.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PLACENTA.2016.08.001
Abstract: Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialised topics. At the 2015 IFPA annual meeting there were 12 themed workshops, three of which are summarized in this report. These workshops related to various aspects of placental biology and collectively covered areas of obesity and the placenta, stem cells of the feto-maternal interface, and placental immunobiology and infection.
Publisher: Wiley
Date: 03-10-2011
DOI: 10.1002/DVDY.22755
Abstract: Early placental development in mice involves patterning of the chorion into distinct layers, though little is understood regarding the interactions that regulate its organization. Here we demonstrate that keratin aggregates found in Mrj(-/-) chorionic trophoblast cells are associated with abnormal cell morphology, collapse of the actin cytoskeleton, E-cadherin and β-catenin misexpression and extracellular matrix (ECM) disorganization. Accordingly, Mrj(-/-) trophoblast cells in vitro are nonadherent and display erratic migratory behavior. These cells also fail to differentiate into syncytiotrophoblast cells since Rhox4b expression, a marker of syncytiotrophoblast progenitors, was maintained and Gcm1, Synb, and Syna expression failed to increase. This differentiation defect was not solely attributable to E-cadherin misexpression or ECM disorganization. However, plating Mrj-deficient cells on exogenous laminin-511 normalized their cell behavior. Lastly, we show that Mrj(-/-) chorions at embryonic day 8.5 have expanded Rhox4b expression domains and do not form normal layers of gene expression suggesting that chorion patterning requires Mrj.
Location: United States of America
No related grants have been discovered for David Natale.