Genetic redundancy of GATA factors in extraembryonic trophoblast lineage ensures progression of both pre and postimplantation mammalian development

Home, Pratik; Kumar, Ram P.; Ganguly, Sudipto; Saha, Biswarup; Milano-Foster, Jessica; Bhattacharya, Bhaswati; Ray, Soma; Gunewardena, Sumedha; Paul, Arindam; Camper, Sally A.; Fields, Patrick E.; Paul, Soumen

doi:10.1242/dev.145318

Cited by 79 publications

(104 citation statements)

References 82 publications

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“…In the mouse placenta, Dlx3 expression is controlled by GATA2 and −3 transcription factors (Home, et al 2017). These transcription factors are also regulators of mouse trophoblast differentiation (Home, et al 2009, Ralston, et al 2010, Ray, et al 2009).…”

Section: Transcription Factors Regulating Ifnt Expressionmentioning

confidence: 99%

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Transcriptional control of IFNT expression

Ezashi¹,

Imakawa²

2017

Reproduction

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Summary Once interferon-tau (IFNT) had been identified as a Type I IFN in sheep and cattle and its functions characterized, numerous studies were conducted to elucidate transcriptional regulation of this gene family. Transfection studies performed largely with human choriocarcinoma cell lines identified regulatory regions of the IFNT gene that appeared responsible for trophoblast-specific expression. The key finding was the recognition that the transcription factor ETS2 bound to a proximal region within the 5/UTR of a bovine IFNT and acted as a strong transactivator. Soon after other transcription factors were identified as cooperative partners. The ETS2-binding site and the nearby AP1 site enable response to intracellular signaling from maternal uterine factors. The AP1 site also serves as a GATA binding site in one of the bovine IFNT genes. The homeobox-containing transcription factor, DLX3, augments IFNT expression combinatorially with ETS2. CDX2 has also been identified as transactivator that binds to a separate site upstream of the main ETS2 enhancer site. CDX2 participates in IFNT epigenetic regulation by modifying histone acetylation status of the gene. The IFNT down-regulation at the time of the conceptus attachment to the uterine endometrium appears correlated with the increased EOMES expression and the loss of other transcription coactivators. Altogether, the studies of transcriptional control of IFNT have provided mechanistic evidence of the regulatory framework of trophoblast-specific expression and critical expression pattern for maternal recognition of pregnancy.

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Section: Transcription Factors Regulating Ifnt Expressionmentioning

confidence: 99%

“…Clearly, further studies are needed to address whether GATA factors directly interact with the IFNT regulatory regions or even modulate IFNT promoter activity in trophoblast. Another possibility is that they act indirectly through other GATA2 and −3 regulated genes, such as DLX3 (Home, et al 2017). …”

Section: Transcription Factors Regulating Ifnt Expressionmentioning

confidence: 99%

Transcriptional control of IFNT expression

Ezashi¹,

Imakawa²

2017

Reproduction

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“…Using the promoter from a specific gene or a chimeric DNA construct to direct Cre expression in specific cells is the key component of the Cre/loxP system. Although several promoters have been used to target transgene expression in trophoblast lineages, to our knowledge very few studies have been conducted using inducible Cre/loxP specifically for placental research . Furthermore, in both of these models, broadly expressed Cre transgenic animals were utilized, complicating the interpretation of the results.…”

Section: Introductionmentioning

confidence: 99%

The platelet‐derived growth factor receptor alpha promoter‐directed expression of cre recombinase in mouse placenta

Wattez

Qiao

Lee

et al. 2019

Developmental Dynamics

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Background Numerous pathologies of pregnancy originate from placental dysfunction. It is essential to understand the functions of key genes in the placenta in order to discern the etiology of placental pathologies. A paucity of animal models that allow conditional and inducible expression of a target gene in the placenta is a major limitation for studying placental development and function. Results To study the platelet‐derived growth factor receptor alpha ( PDGFRα )‐directed and tamoxifen‐induced Cre recombinase expression in the placenta, PDGFRα‐CreER mice were crossed with mT/mG dual‐fluorescent reporter mice. The expression of endogenous membrane‐localized enhanced green fluorescent protein (mEGFP) and/or dTomato in the placenta was examined to identify PDGFRα promoter‐directed Cre expression. Pregnant PDGFRα‐CreER ;mT/mG mice were treated with tamoxifen at various gestational ages. Upon tamoxifen treatment, reporter protein mEGFP was observed in the junctional zone (JZ) and chorionic plate (CP). Furthermore, a single dose of tamoxifen was sufficient to induce the recombination. Conclusions PDGFRα‐CreER expression is restricted to the JZ and CP of mouse placentas. PDGFRα‐CreER mice provide a useful tool to conditionally knock out or overexpress a target gene in these regions of the mouse placenta.

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“…They are implicated in the regulation of the expression of several trophoblast-specific genes, including prolactin hormone Placental lactogen I (Prl3d1, Pl1) and the angiogenic factor Proliferin (Prl2c2, Plf), which play an essential role in the neovascularization of the placenta (14,15). Recently we demonstrated that simultaneous knockout of both Gata2 and Gata3 in trophoblast lineage severely affects placental development (16). Also, the double gene knock-out resulted in significant developmental defects in the embryo proper leading to very early embryonic lethality (16).…”

Section: Introductionmentioning

confidence: 99%

Trophoblast paracrine signaling regulates placental hematoendothelial niche

Home

Ghosh

Kumar

et al. 2019

Preprint

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The placenta acts as a major organ for hematopoiesis. It is believed that placental hematopoietic stem and progenitor cells (HSPCs) migrate to the fetal liver to ensure optimum hematopoiesis in the developing embryo. The labyrinth vasculature in a mid-gestation mouse placenta provides a niche for the definitive hematopoietic stem cell (HSC) generation and expansion. It has been proposed that these processes are regulated by a host of paracrine factors secreted by trophoblast giant cells (TGCs) at the maternal-fetal interface. However, the molecular mechanism by which the TGCs regulate the hematoendothelial niche in a developing placenta is yet to be defined. Using a TGC-specific Gata2 and Gata3 double knockout mouse model, weshow that the loss of GATA2 and GATA3 at the TGC layer leads to fetal growth retardation and embryonic death due to disruptions in the delicate hematopoietic-angiogenic balance in the developing placenta. Using single-cell RNA-Seq analyses, we also show that the loss of GATA factors in the TGCs results in the loss of HSC population within the placental labyrinth and is associated with defective placental angiogenesis. Interestingly, we also found that this TGCspecific GATA factor-loss leads to impaired differentiation and distribution of trophoblast progenitor cells. Our study helps to define the GATA-dependent non-autonomous signaling mechanisms of the primary parietal trophoblast giant cells by which it regulates the delicate hematopoietic-angiogenic balance in the developing placenta.

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Genetic redundancy of GATA factors in extraembryonic trophoblast lineage ensures progression of both pre and postimplantation mammalian development

Cited by 79 publications

References 82 publications

Transcriptional control of IFNT expression

Transcriptional control of IFNT expression

The platelet‐derived growth factor receptor alpha promoter‐directed expression of cre recombinase in mouse placenta

Trophoblast paracrine signaling regulates placental hematoendothelial niche

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