<i>Xenopus er71</i> is involved in vascular development

Neuhaus, Herbert; Müller, Frank; Hollemann, Thomas

doi:10.1002/dvdy.22487

Cited by 32 publications

(26 citation statements)

References 26 publications

(26 reference statements)

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“…Given that deficiency in either Scl or Etv2 results in a complete hematopoietic defect, this transcriptional control of one essential gene by another essential gene appears to be an unusual mode of regulation for a developmental program and seems to have progressively evolved over time. In Xenopus, ETV2 does not appear to control hematopoiesis [37,38]. Instead FLI1, another Ets family member, was shown to act at the top of the transcriptional network controlling blood and endothelial development [39].…”

Section: Discussionmentioning

confidence: 99%

The Flk1-Cre-Mediated Deletion of ETV2 Defines Its Narrow Temporal Requirement During Embryonic Hematopoietic Development

et al. 2012

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During embryonic development, the emergence of hematopoiesis and vasculogenesis is tightly associated, with many transcription factors implicated in both developmental processes. Among those factors, ETV2 acts at the top of the hierarchy and controls the formation of both lineages. However, it is not known at which stage of mesoderm development ETV2 is acting and whether ETV2 activity is further required once mesodermal precursors have been specified to the hematopoietic and endothelial fates. In this study, we characterize the developmental window during which ETV2 expression is required for hematopoietic and endothelial development. Using cre-mediated deletion of ETV2, we demonstrate that ETV2 is acting prior to or at the time of FLK1 expression in mesodermal precursors to initiate the hematopoietic and endothelial program. Using the in vitro differentiation of embryonic stem cells as a model system, we further show that ETV2 re-expression in Etv2

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Section: Discussionmentioning

confidence: 99%

The Flk1-Cre-Mediated Deletion of ETV2 Defines Its Narrow Temporal Requirement During Embryonic Hematopoietic Development

et al. 2012

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“…Finally, etsrp is required for the vascular endothelial and primitive myeloid cells in zebrafish (Sumanas and Lin, 2006;Sumanas et al, 2008). It has a functional homolog in both mammals (Lee et al, 2008;Kataoka et al, 2011) and Xenopus (Neuhaus et al, 2010;Salanga et al, 2010). In mouse, knockout of Etsrp (Etv2) results in complete depletion of endothelium and blood cells, indicating that it plays a role in the induction of bipotent progenitors.…”

Section: Tal1mentioning

confidence: 99%

Hematopoiesis

Jagannathan-Bogdan

Zon²

2013

Development

288

208

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Hematopoiesis – the process by which blood cells are formed – has been studied intensely for over a century using a variety of model systems. There is conservation of the overall hematopoietic process between vertebrates, although some differences do exist. Over the last decade, the zebrafish has come to the forefront as a new model in hematopoiesis research, as it allows the use of large-scale genetics, chemical screens and transgenics. This comparative approach to understanding hematopoiesis has led to fundamental knowledge about the process and to the development of new therapies for disease. Here, we provide a broad overview of vertebrate hematopoiesis. We also highlight the benefits of using zebrafish as a model.

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“…Although zebrafish etsrp morphants were reported to be rescued by injecting etsrp mRNA, the effects of Etv2 homolog knock-down on hematopoiesis in zebrafish or Xenopus are smaller than in mice. 23,24 To determine whether Etv2 can rescue the loss of HPCs and ECs in mice, we introduced an Etv2 transgene into Etv2-null ESCs (Figure 3Da). It is assumed that ESC differentiation cannot fully recapitulate the embryonic hematopoiesis, however, it has been used at least to mimic the primitive part of hematopoiesis.…”

Section: Etv2 Reexpression In Etv2 ؊/؊ Escs Restores Hemato-endothelimentioning

confidence: 99%

Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm

Kataoka

Hayashi²,

Nakagawa³

et al. 2011

Blood

161

205

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Etv2 (Ets IntroductionBased on observations that several single-gene mutations severely affect both endothelial cell (EC) and hematopoietic cell (HPC) lineages, ECs and HPCs are proposed to originate from common precursors called hemangioblasts. 1,2 In zebrafish, cloche is the most classic mutant affecting both ECs and HPCs. 3,4 Deleting Flk-1, a major signaling receptor for VEGF, in mice causes defects in both ECs and HPCs. 5,6 However, in vitro differentiation of Flk-1-null embryonic stem cells (ESCs) generates both ECs and HPCs, albeit at much lower efficiencies. 7,8 These findings demonstrate that Flk-1 is dispensable for the differentiation of hemato-endothelial precursors but is required for the proliferation of these progenitor cells.Etv2 (Ets variant 2), identified in zebrafish as etsrp71, has been reported to be a key molecule for investigating In etsrp71 mutants, vasculogenesis and myelopoiesis are affected, leaving primitive erythropoiesis relatively intact. Conversely, overexpression of etsrp71 induces ectopic EC generation indicating a strong vasculogenic potential of etsrp71. 12 In mice, Etv-2 disruption results in a lack of Flk-1 expression, leading to the total loss of ECs and HPCs. 10,13 In ESCs, Etv2 overexpression up-regulates Flk-1 and subsequent EC generation. 10 From these results, Etv2 was hypothesized to be induced by bone morphogenic protein (BMP), Notch, and Wnt signaling and then transactivate Flk1. However, the phenotype discrepancy between the etsrp71 zebrafish mutant and Etv2-knockout mice raised the possibility that Etv2 may have more complex functions than proposed as an activator of Flk-1. Recent studies in zebrafish showed that, in addition to Flk-1, EC or HPC genes can also be up-regulated more robustly by Etv2. 14,15 Using Etv2 Venus knock-in mice and Etv2-null ESC lines (Etv2-Venus ϩ/Ϫ and Etv2 Ϫ/Ϫ , respectively), the role of Etv2 and downstream target genes in EC and HPC development from mesoderm were investigated in the present study. Methods Etv2-Venus ESCs and miceTargeting vector for the mouse Etv-2 locus was constructed using the Gateway cassette vector system containing Venus and Cre removable Neo resistance cassette. 16 Genomic sequences corresponding to 111658-119169 (accession number 167978.4) on the 5Јside and 119172-122639 (accession number 167978.4) on the 3Ј side were used as homology arms for recombination, and Venus was subcloned in-frame into the endogenous Etv2 allele. The resulting targeting construct and TT2 ESCs were used to generate Etv2-Venus knock-in mice (CDB0675K). Original and modified Etv2 loci are depicted in supplemental Figure 1 (available on the Blood Web site; see the Supplemental Materials link at the top of the online article). Etv2 locus on the other allele was targeted to generate homozygous Etv2-null ESCs. These Etv2-Venus mice or gene-trap line 141H7 were used to generate Etv2-null embryos. 13 RNA isolation and expression profilingRNA was purified using the RNeasy MinElute column (QIAGEN) and reverse transcribed by Revatrace (TOYOBO). ...

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Xenopus er71 is involved in vascular development

Cited by 32 publications

References 26 publications

The Flk1-Cre-Mediated Deletion of ETV2 Defines Its Narrow Temporal Requirement During Embryonic Hematopoietic Development

The Flk1-Cre-Mediated Deletion of ETV2 Defines Its Narrow Temporal Requirement During Embryonic Hematopoietic Development

Hematopoiesis

Etv2/ER71 induces vascular mesoderm from Flk1+PDGFRα+ primitive mesoderm

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