Interplay among Etsrp/ER71, Scl, and Alk8 signaling controls endothelial and myeloid cell formation

Sumanas, Saulius; Gomez, Gustavo A.; Zhao, Yan; Park, Changwon; Choi, Kyunghee; Lin, Shuo

doi:10.1182/blood-2007-09-110569

Cited by 106 publications

(152 citation statements)

References 36 publications

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“…Recent reports revealing Nkx2-5 expression in the endocardium (10) and the endocardial fate of the Nkx2-5-expressing cardiac progenitors (4-6) support the hypothesis that Nkx2-5 is an important regulator of the endothelial/ endocardial lineage during cardiogenesis although the molecular mechanisms are unknown. Recent studies in mice (24) and zebrafish (25,26) have reported that Etsrp71/ER71 is essential for the genesis of endothelial/endocardial lineage in the developing embryos. However, the transcriptional regulation of Etsrp71 was unclear.…”

Section: Discussionmentioning

confidence: 99%

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Ferdous

Caprioli²,

Iacovino

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

197

298

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Recent studies support the existence of a common progenitor for the cardiac and endothelial cell lineages, but the underlying transcriptional networks responsible for specification of these cell fates remain unclear. Here we demonstrated that Ets-related protein 71 (Etsrp71), a newly discovered ETS family transcription factor, was a novel downstream target of the homeodomain protein, Nkx2-5. Using genetic mouse models and molecular biological techniques, we demonstrated that Nkx2-5 binds to an evolutionarily conserved Nkx2-5 response element in the Etsrp71 promoter and induces the Etsrp71 gene expression in vitro and in vivo. Etsrp71 was transiently expressed in the endocardium/endothelium of the developing embryo (E7.75-E9.5) and was extinguished during the latter stages of development. Using a gene disruption strategy, we found that Etsrp71 mutant embryos lacked endocardial/endothelial lineages and were nonviable. Moreover, using transgenic technologies and transcriptional and chromatin immunoprecipitation (ChIP) assays, we further established that Tie2 is a direct downstream target of Etsrp71. Collectively, our results uncover a novel functional role for Nkx2-5 and define a transcriptional network that specifies an endocardial/endothelial fate in the developing heart and embryo.cardiac progenitor cells ͉ endocardium ͉ Etsrp71 ͉ Tie2 ͉ cardiac development

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Section: Discussionmentioning

confidence: 99%

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Ferdous

Caprioli²,

Iacovino

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

197

298

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“…34 Sumanas et al recently reported the dependence of myeloid gene expression on etsrp in the anterior hemangioblast population in zebrafish embryos. 35 They showed, by etsrpMO knockdown that myeloid markers, such as lcp1, mpx, and pu.1, were reduced and that overexpression of etsrp could upregulate lcp1 and pu.1 expression. However, anterior expression of endothelial markers, such as flk1, was not analyzed.…”

Section: A Role For Etsrp In Hemangioblast Formationmentioning

confidence: 99%

Genome-Wide Analysis of the Zebrafish ETS Family Identifies Three Genes Required for Hemangioblast Differentiation or Angiogenesis

Liu

Patient

2008

Circulation Research

108

118

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Abstract-ETS domain transcription factors have been linked to hematopoiesis, vasculogenesis, and angiogenesis.However, their biological functions and the mechanisms of action, remain incompletely understood. Here, we have performed a systematic analysis of zebrafish ETS domain genes and identified 31 in the genome. Detailed gene expression profiling revealed that 12 of them are expressed in blood and endothelial precursors during embryonic development. Combined with a phylogenetic tree assay, this suggests that some of the coexpressed genes may have redundant or additive functions in these cells. Loss-of-function analysis of 3 of them, erg, fli1, and etsrp, demonstrated that erg and fli1 act cooperatively and are required for angiogenesis possibly via direct regulation of an endothelial cell junction molecule, VE-cadherin, whereas etsrp is essential for primitive myeloid/endothelial progenitors (hemangioblasts) in zebrafish. Taken together, these results provide a global view of the ETS genes in the zebrafish genome during embryogenesis and provide new insights on the functions and biology of erg, fli1, and etsrp, which could be applicable to higher vertebrates, including mice and humans. (Circ Res. 2008;103:1147-1154.)Key Words: zebrafish Ⅲ gene duplication Ⅲ ETS transcription factors Ⅲ hemangioblast Ⅲ angiogenesis Z ebrafish has been recognized as an excellent genetic and developmental biology model to study hematopoiesis and vessel development. Large numbers of genetic mutants and transgenic lines in both blood and endothelial lineages have become available. More importantly, developmental mechanisms, including the functions of many known important regulators involved in both blood and vessel development, are conserved between higher vertebrates and zebrafish. 1 It has been proposed that hematopoietic and endothelial cells share a common progenitor, termed the hemangioblast. 2 This idea was initially conceived from the observation that these 2 cell types develop in close proximity within the embryo. 3 Coexpression of many important regulators of hematopoiesis and vasculogenesis in early embryos further supports the existence of a common progenitor for hematopoietic and endothelial cells. Furthermore, loss of function of several of these regulators, including the zebrafish cloche (clo) mutant, affects both cell types. 4 -7 Recent work by us and others subsequently showed that several important hematopoietic and endothelial regulators in mammals, such as Scl/Tal1 and Lmo2, also play similar roles in zebrafish. 8 -10 ETS domain genes encode a super family of transcription factors organized into 11 subfamilies based on domain structures, which are conserved from worm and fly to mammals. 11 These transcription factors are involved in cell fate specification, proliferation, migration, and differentiation during embryonic development and adulthood and have been linked with diverse biological processes, from hematopoiesis, vasculogenesis, and angiogenesis to neurogenesis. Many important blood and endothelial regul...

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“…ETS factors can induce expression of endothelial specific genes such as flk1/vegfr2 and vascular endothelial cadherin (vecdn), and loss of function for these factors causes defects in endothelial cell behavior (Wakiya et al 1996;Chen et al 1997;Lelievre et al 2000;Nakano et al 2000). Loss of function of the ETS factor Etv2 (Etsrp71) in the mouse or frog and its ortholog, estrp, in zebrafish results in defects in vascular formation and hematopoietic differentiation (Sumanas and Lin 2006;Pham et al 2007;Sumanas et al 2008;Salanga et al 2010). Although in vivo loss of function of the ETS factors ets1 or friend leukemia integration 1 ( fli1) does not cause significant defects in vascular development in mouse or zebrafish embryos, combinatorial knockdown of four vascular ETS factors, fli1a, fli1b, ets1, and ets1-related protein (etsrp) in zebrafish leads to defects in endothelial cell specification and differentiation (Pham et al 2007).…”

Section: Origin and Specification Of Endothelial Precursorsmentioning

confidence: 99%

Vascular Development in the Zebrafish

Gore¹,

Monzo²,

Young³

et al. 2012

Cold Spring Harbor Perspectives in Medicine

230

166

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The zebrafish has emerged as an excellent vertebrate model system for studying blood and lymphatic vascular development. The small size, external and rapid development, and optical transparency of zebrafish embryos are some of the advantages the zebrafish model system offers. Multiple well-established techniques have been developed for imaging and functionally manipulating vascular tissues in zebrafish embryos, expanding on and amplifying these basic advantages and accelerating use of this model system for studying vascular development. In the past decade, studies performed using zebrafish as a model system have provided many novel insights into vascular development. In this article we discuss the amenability of this model system for studying blood vessel development and review contributions made by this system to our understanding of vascular development.

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Interplay among Etsrp/ER71, Scl, and Alk8 signaling controls endothelial and myeloid cell formation

Cited by 106 publications

References 36 publications

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo

Genome-Wide Analysis of the Zebrafish ETS Family Identifies Three Genes Required for Hemangioblast Differentiation or Angiogenesis

Vascular Development in the Zebrafish

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