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Dlx3 placenta

Sha Li, Mark S Roberson
Placental growth factor (PGF) is abundantly expressed by trophoblast cells within human placentae and is important for trophoblast development and placental vascularization. Circulating maternal serum levels of PGF are dynamically upregulated across gestation in normal pregnancies, whereas low circulating levels and placental production of PGF have been implicated in the pathogenesis of preeclampsia and other gestational diseases. However, the underlying molecular mechanism of regulating PGF expression in the human placenta remains poorly understood...
October 2017: Journal of Cellular Physiology
Xi Tian, Kate Anthony, Thomas Neuberger, Francisco J Diaz
Zinc is an essential nutrient for optimal fertility, but the effects of preconception zinc deficiency on postimplantation development are not known. Female mice were fed a control or a zinc-deficient diet (ZDD) for 4-5 days before ovulation (preconception). Embryonic and/or placental development were evaluated on Days 3.5, 6.5, 10.5, 12.5, and 16.5 of pregnancy. The findings show a decrease in embryo length (31%, Day 10.5; 13%, Day 12.5; 10%, Day 16.5) and weight (23%, Day 16.5) in embryos from mothers fed a ZDD preconception...
April 2014: Biology of Reproduction
Amy Chui, Bill Kalionis, Mohamed Abumaree, Melanie Cocquebert, Thierry Fournier, Daniele Evain-Brion, Shaun P Brennecke, Padma Murthi
Human idiopathic fetal growth restriction (FGR) is associated with placental insufficiency. Previously, we reported that the expression of homeobox gene Distal-less 3 (DLX3) is increased in idiopathic FGR placentae and is a regulator of villous trophoblast differentiation. Here, we identify the downstream targets of DLX3 in trophoblast-derived cell lines. We modelled the high levels of DLX3 in FGR using an over-expression plasmid construct and complemented this using short-interference RNA (siRNA) for inactivation in cultured cells...
September 5, 2013: Molecular and Cellular Endocrinology
Patricia A Clark, Jianjun Xie, Sha Li, Xuesen Zhang, Scott Coonrod, Mark S Roberson
Matrix metalloproteinases (MMPs) are enzymes that regulate extracellular matrix composition and contribute to cell migration. Microarray studies in mouse placenta suggested that MMP-9 transcript abundance was dependent on distal-less 3 (Dlx3), a placental-specific transcriptional regulator; however, it was not clear if this was a direct or indirect effect. Here we investigate mechanism(s) for Dlx3-dependent MMP-9 gene transcription and gelatinase activity in placental trophoblasts. Initial studies confirmed that MMP-9 activity was reduced in placental explants from Dlx3(-/-) mice and that murine MMP-9 promoter activity was induced by Dlx3 overexpression...
July 15, 2013: American Journal of Physiology. Cell Physiology
Kenta Sumiyama, Tsutomu Miyake, Jane Grimwood, Andrew Stuart, Mark Dickson, Jeremy Schmutz, Frank H Ruddle, Richard M Myers, Chris T Amemiya
The mammalian Dlx3 and Dlx4 genes are configured as a bigene cluster, and their respective expression patterns are controlled temporally and spatially by cis-elements that largely reside within the intergenic region of the cluster. Previous work revealed that there are conspicuously conserved elements within the intergenic region of the Dlx3-4 bigene clusters of mouse and human. In this paper we have extended these analyses to include 12 additional mammalian taxa (including a marsupial and a monotreme) in order to better define the nature and molecular evolutionary trends of the coding and non-coding functional elements among morphologically divergent mammals...
December 2012: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
P A Clark, J L Brown, S Li, A K Woods, L Han, J L Sones, R L Preston, T L Southard, R L Davisson, M S Roberson
Distal-less 3 (Dlx3)(-/-) mice die at E9.5 presumably due to an abnormal placental phenotype including reduced placental vasculature and secretion of placental growth factor. To examine the role of Dlx3 specifically within the epiblast, Dlx3 conditional knockout mice were generated using an epiblast-specific Meox2(CreSor) allele. Dlx3(-/fl), Meox2(CreSor) animals were born at expected frequencies and survived to weaning providing indirect evidence that loss of Dlx3 within the trophoectoderm plays a critical role in fetal survival in the Dlx3(-/-) mouse...
October 2012: Placenta
Amy Chui, Charmaine Tay, Melanie Cocquebert, Penelope Sheehan, Niroshani A Pathirage, Susan Donath, Thierry Fournier, Josette Badet, Daniele Evain-Brion, Shaun P Brennecke, Bill Kalionis, Padma Murthi
Human idiopathic foetal growth restriction (FGR) is frequently associated with placental insufficiency. In our previous studies, we have reported the isolation and characterisation of the homeobox gene Distal-less 3 (DLX3) in the human placenta. In this study, we have investigated the level of DLX3 expression in idiopathic FGR-affected placentae and determined its functional role in villous trophoblast differentiation. FGR-affected placentae (n = 25) were collected based on well-defined clinical criteria and matched for gestation with control uncomplicated pregnancies (n = 25)...
March 2012: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
S A Degrelle, P Murthi, D Evain-Brion, T Fournier, I Hue
The differentiation of the trophoblast is marked in ruminants by the formation of binucleated cells (BNC). They appear from pre-implantation onwards but the molecular mechanisms underlying their differentiation remain largely unexplored. Taking advantage of our recent data, we analyzed the expression pattern of DLX3 and PPARG that are known regulators of early placenta formation and extended our analysis to one of their potential regulators, SP1. Our study is the first to demonstrate the co-expression of DLX3, PPARG and SP1 in bovine BNC nuclei...
November 2011: Placenta
A Chui, D A Evseenko, S P Brennecke, J A Keelan, B Kalionis, P Murthi
Dlx3, a member of the large homeobox gene family of transcription factors, is important for murine placental development. Targeted deletion of Dlx3 in the mouse results in embryonic death due to placental failure. This study investigated the role of human DLX3 in villous cytotrophoblast (VCT) differentiation in the placenta. Primary VCT from human term placentae, which spontaneously differentiate when maintained in culture over 72 h, showed a significant increase in mRNA and protein expression of DLX3 and 3βHSD...
October 2011: Placenta
Antonella Di Costanzo, Luisa Festa, Giuseppina Roscigno, Maria Vivo, Alessandra Pollice, Maria Morasso, Girolama La Mantia, Viola Calabrò
The homeodomain transcription factors play crucial roles in many developmental processes ranging from organization of the body plan to differentiation of individual tissues. The homeodomain protein Distal-less-3 (DLX3) has an essential role in epidermal stratification and development of ectodermal appendages, placenta and bones. A four-nucleotide deletion in the human DLX3 gene is etiologic for the human hereditary tricho-dento-osseous (TDO) ectodermal dysplasia, a dominant syndrome characterized by abnormalities in hair, nails, teeth, and bones...
August 2011: Journal of Cellular Physiology
A Chui, N A Pathirage, B Johnson, M Cocquebert, T Fournier, D Evain-Brion, B Roald, U Manuelpillai, S P Brennecke, B Kalionis, P Murthi
DLX3, a member of the large homeobox gene family of transcription factors, is necessary for normal placentation. Targeted deletion of dlx3 in mouse resulted in embryonic death due to placental failure. This study demonstrates the presence of DLX3 mRNA expression in human first trimester and term placental tissue, cultured trophoblast-like cell lines and in isolated primary villous and extravillous trophoblast cells. Using an ovine polyclonal antibody, the spatial distribution was identified for DLX3 in human placental tissues, trophoblast cell lines and in freshly isolated primary trophoblast cells...
August 2010: Placenta
Yohei Hayashi, Miho Kusuda Furue, Satoshi Tanaka, Michiko Hirose, Noriko Wakisaka, Hiroki Danno, Kiyoshi Ohnuma, Shiho Oeda, Yuko Aihara, Kunio Shiota, Atsuo Ogura, Shoichi Ishiura, Makoto Asashima
Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers...
May 2010: In Vitro Cellular & Developmental Biology. Animal
P Murthi, U Hiden, G Rajaraman, H Liu, A J Borg, F Coombes, G Desoye, S P Brennecke, B Kalionis
Angiogenesis is fundamental to normal placental development and aberrant angiogenesis contributes substantially to placental pathologies. The complex process of angiogenesis is regulated by transcription factors leading to the formation of endothelial cells that line the microvasculature. Homeobox genes are important transcription factors that regulate vascular development in embryonic and adult tissues. We have recently shown that placental homeobox genes HLX, DLX3, DLX4, MSX2 and GAX are expressed in placental endothelial cells...
July 2008: Placenta
Ravid Sasson, Sang H Luu, Varykina G Thackray, Pamela L Mellon
The human glycoprotein hormone alpha-subunit (alphaGSU) gene is transcriptionally regulated by glucocorticoids in a cell type-specific fashion. In direct contrast to repression of alphaGSU by glucocorticoids in placenta, glucocorticoid receptor (GR) modulation in the pituitary is little understood. We show that glucocorticoids stimulate the alphaGSU promoter in immortalized pituitary gonadotrope-derived LbetaT2 cells, whereas estrogens, androgens, and progestins have no significant effect. Moreover, GR acts in a dose-dependent manner at physiological concentrations of glucocorticoids...
July 2008: Endocrinology
J Timothy Wright, Sung P Hong, Darrin Simmons, Bill Daly, Daniel Uebelhart, Hans U Luder
The distal-less homeobox gene DLX3 is expressed in a variety of tissues including placenta, skin, hair, teeth, and bone. Mutation of DLX3 (c.571_574delGGGG) causes the tricho-dento-osseous syndrome (TDO), characterized by abnormal hair, teeth, and bone. Evaluation of a kindred segregating the DLX3 c.561_562delCT mutation revealed distinct changes in the hair, teeth, and bones as has been observed with the DLX3 c.571_574delGGGG mutation. Previously, the DLX3 c.561_562delCT mutation was associated with autosomal dominant amelogenesis imperfecta with taurodontism...
February 1, 2008: American Journal of Medical Genetics. Part A
Li Han, Monica Dias Figueiredo, Kathie A Berghorn, Terri N Iwata, Patricia A Clark-Campbell, Ian C Welsh, Wei Wang, Timothy P O'brien, David M Lin, Mark S Roberson
Dlx3, a homeodomain transcription factor, is essential for placental development in the mouse. The Dlx3(-/-) mouse embryo dies at embryonic d 9.5-10 putatively due to placental failure. To develop a more comprehensive understanding of the gene profile regulated by Dlx3, microarray analysis was used to determine differences in gene expression within the placenta of Dlx3(+/+) and Dlx3(-/-) mice. Array analysis revealed differential expression of 401 genes, 33 genes in which signal to log ratio values of null/wild-type were lower than -0...
March 2007: Endocrinology
Kathie A Berghorn, Patricia A Clark-Campbell, Li Han, Michael McGrattan, Robert S Weiss, Mark S Roberson
Dlx3 (Distal-less 3) is a homeobox-containing transcription factor required for normal placental development in mice. Here we demonstrate that Dlx3 interacts with Smad6, a member of a larger family of transcriptional regulators generally thought to regulate transforming growth factor beta/bone morphogenetic protein signaling. Immunocytochemical and immunoprecipitation studies demonstrate overlapping nuclear localization and physical interaction between Dlx3 and Smad6 in human choriocarcinoma cells and in differentiated trophoblasts from human placenta...
July 21, 2006: Journal of Biological Chemistry
P Murthi, M So, N M Gude, V L Doherty, S P Brennecke, B Kalionis
Angiogenesis is fundamental to normal placental development. Aberrant angiogenesis within the placental terminal villi is a characteristic of significant placental pathologies and includes structural and vascular abnormalities as well as altered endothelial cell function, which substantially impacts on maternal-fetal exchange. Homeobox gene transcription factors regulate vascular development in embryonic and adult tissues, but their role in the placental microvasculature is not well known. In this study, we isolated and enriched human placental microvascular endothelial cells (PLEC) by a perfusion-based method and compared homeobox gene expression between PLEC and macrovascular human umbilical vein endothelial cells (HUVEC)...
February 2007: Placenta
K A Berghorn, P A Clark, B Encarnacion, C J Deregis, J K Folger, M I Morasso, M J Soares, M W Wolfe, M S Roberson
Distal-less 3 (Dlx3) is a homeobox factor that functions as a placental-specific transcriptional regulator. Dlx3 null mice (-/-) have compromised placental development and do not survive in utero past embryonic day (E) 9.5. The current studies were undertaken to examine the expression of Dlx3 in mouse placenta during gestation, and to determine whether Dlx3 was involved in placental progesterone production. Dlx3 was not detectable at E8.5 but was detected in E9.5 placenta with continuing but diminished expression through E15...
August 2005: Journal of Endocrinology
Manja P Holland, Stuart P Bliss, Kathie A Berghorn, Mark S Roberson
The homeodomain protein Distal-less 3 (Dlx3) is essential for normal placental development in mice. Dlx3-null mice die by embryonic day 10.0 due to placental failure. The aim of our studies was to examine the transcriptional regulation and expression of Dlx3 in choriocarcinoma cell lines and primary trophoblasts from human placenta. A Dlx3 promoter fragment coupled to a luciferase reporter gene was sufficient to increase luciferase activity more than 11-fold over a luciferase control vector in choriocarcinoma cells, but not in a heterologous gonadotrope cell line...
March 2004: Endocrinology
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