Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta

Chui, Amy; Pathirage, Niroshani; Johnson, Brett V.; Fournier, Thierry; Évain-Brion, D.; Roald, Borghild; Manuelpillai, Ursula; Brennecke, Shaun P.; Kalionis, Bill; Murthi, Padma

doi:10.1016/j.placenta.2010.05.003

Cited by 32 publications

(33 citation statements)

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“…We and others have previously demonstrated that PGF expression in human trophoblast-derived cells requires both transcription factors of DLX3 and Glial cell missing (GCM)1 31, 32, 40 . Correlated with this finding, expression patterns of DLX3, GCM1 and PGF overlap remarkably within human placental tissues examined at term; most abundantly in villous cytotrophoblasts (CTB), syncytiotrophoblasts (STB) and extravillous trophoblasts (EVT) in the proximal regions of CTB columns 41–44 . Expression of DLX3 and PGF was additionally observed in endothelial cells surrounding fetal capillaries, highlighting the potential involvement of DLX3 in fetoplacental angiogenesis 41, 43, 44 .…”

Section: Introductionmentioning

confidence: 61%

“…Correlated with this finding, expression patterns of DLX3, GCM1 and PGF overlap remarkably within human placental tissues examined at term; most abundantly in villous cytotrophoblasts (CTB), syncytiotrophoblasts (STB) and extravillous trophoblasts (EVT) in the proximal regions of CTB columns 41–44 . Expression of DLX3 and PGF was additionally observed in endothelial cells surrounding fetal capillaries, highlighting the potential involvement of DLX3 in fetoplacental angiogenesis 41, 43, 44 . Importantly, decreased levels of DLX3 and GCM1 have been reported in placentae complicated with PE, in which PGF is dysregulated 45, 46 .…”

Section: Introductionmentioning

confidence: 61%

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DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

Roberson

2017

Sci Rep

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The placental transcription factors Distal-less 3 (DLX3) and Glial cell missing-1 (GCM1) have been shown to coordinate the specific regulation of PGF in human trophoblast cell lines. While both factors independently have a positive effect on PGF gene expression, when combined, DLX3 acts as an antagonist to GCM. Despite this understanding, potential mechanisms accounting for this regulatory interaction remain unexplored. We identify physical and functional interactions between specific domains of DLX3 and GCM1 in human trophoblast-derived cells by performing immunoprecipitation and mammalian one hybrid assays. Studies revealed that DLX3 binding reduced the transcriptional activity of GCM1, providing a mechanistic explanation of their functional antagonism in regulating PGF promoter activity. The DLX3 homeodomain (HD) was essential for DLX3-GCM1 interaction, and that the HD together with the DLX3 amino- or carboxyl-terminal domains was required for maximal inhibition of GCM1. Interestingly, a naturally occurring DLX3 mutant that disrupts the carboxyl-terminal domain leading to tricho-dento-osseous syndrome in humans displayed activities indistinguishable from wild type DLX3 in this system. Collectively, our studies demonstrate that DLX3 physically interacts with GCM1 and inhibits its transactivation activity, suggesting that DLX3 and GCM1 may form a complex to functionally regulate placental cell function through modulation of target gene expression.

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Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 61%

DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

Roberson

2017

Sci Rep

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“…Antibody binding was visualized using horseradish peroxidase-conjugated goat anti-rabbit secondary antibody (Invitrogen/Life Technologies), followed by autoradiography using the ECL-Western Chemiluminescence Detection Kit (GE Healthcare). Total protein load on the gel was determined by Coomassie staining, and the immunoreactive NKX3.1 protein was analyzed by scanning densitometry (ImageQuant, GE Healthcare) as described previously (25,26,33,34).…”

Section: Immunoblottingmentioning

confidence: 99%

An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction

Murthi¹,

Brouillet²,

Pratt³

et al. 2015

Mol Med

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“…We carried out the first screening of a 32-week placental cDNA library for homeobox genes, which led to the isolation of DLX4, MSX2, GAX , and HLX (Quinn et al, 1997; Rajaraman et al, 2008). Immunohistochemical analyses identified the localisation of these homeobox genes in both trophoblasts and endothelial cells of the human placenta (Murthi et al, 2006a; Rajaraman et al, 2008; Chui et al, 2010). …”

Section: Homeobox Genes In the Placentamentioning

confidence: 99%

Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

2014

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Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. Homeobox genes comprise an important family of transcription factors, which are characterized by a well conserved DNA binding motif; the homeodomain. The specificity of the homeodomain allows the transcription factor to bind to the promoter regions of batteries of target genes and thereby regulates their expression. Target genes identified for homeodomain proteins have been shown to control fundamental cell processes such as proliferation, differentiation, and apoptosis. We and others have reported that homeobox genes are expressed in the placental vasculature, but our knowledge of their downstream target genes is limited. This review highlights the importance of studying the cellular and molecular mechanisms by which homeobox genes and their downstream targets may regulate important vascular cellular processes such as proliferation, migration, and endothelial tube formation, which are essential for placental vasculogenesis and angiogenesis. A better understanding of the molecular targets of homeobox genes may lead to new therapies for aberrant angiogenesis associated with clinically important pregnancy pathologies, including fetal growth restriction and preeclampsia.

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Homeobox gene distal-less 3 is expressed in proliferating and differentiating cells of the human placenta

Cited by 32 publications

References 33 publications

DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

DLX3 interacts with GCM1 and inhibits its transactivation-stimulating activity in a homeodomain-dependent manner in human trophoblast-derived cells

An EG-VEGF-Dependent Decrease in Homeobox Gene NKX3.1 Contributes to Cytotrophoblast Dysfunction: A Possible Mechanism in Human Fetal Growth Restriction

Analysis of homeobox gene action may reveal novel angiogenic pathways in normal placental vasculature and in clinical pregnancy disorders associated with abnormal placental angiogenesis.

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