Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis

Michael P. Craig; Viktorija Grajevskaja; Hsin-Kai Liao; Jorune Balciuniene; Stephen C. Ekker; Joo-Seop Park; Jeffrey J. Essner; Darius Balciunas; Saulius Sumanas

doi:10.1161/ATVBAHA.114.304768

Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis

Michael P. Craig, Viktorija Grajevskaja, Hsin-Kai Liao, Jorune Balciuniene, Stephen C. Ekker, Joo-Seop Park, Jeffrey J. Essner, Darius Balciunas, Saulius Sumanas

Research output: Contribution to journal › Article › peer-review

Abstract

<h3 id="x-x-d3e238"> Objective; </h3> The E26 transformation-specific domain transcription factor Etv2 / Etsrp / ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis. <h3 id="x-x-d3e253"> Approach and Results; </h3> Zebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b . Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b , but not fli1a , induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites. <h3 id="x-x-d3e303"> Conclusions; </h3> Our data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.

Original language	American English
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	35
DOIs	https://doi.org/10.1161/ATVBAHA.114.304768
State	Published - Apr 1 2015

Keywords

angiogenesis
ETS transcription factor
vasculogenesis
zebrafish

Disciplines

Biochemistry, Biophysics, and Structural Biology
Life Sciences
Molecular Biology

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427907/

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@article{1855e7def70146dfa54fa2792ad93e7a,

title = "Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis",

abstract = " Objective; The E26 transformation-specific domain transcription factor Etv2 / Etsrp / ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis. Approach and Results; Zebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b . Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b , but not fli1a , induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites. Conclusions; Our data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.",

keywords = "angiogenesis, ETS transcription factor, vasculogenesis, zebrafish",

author = "Craig, {Michael P.} and Viktorija Grajevskaja and Hsin-Kai Liao and Jorune Balciuniene and Ekker, {Stephen C.} and Joo-Seop Park and Essner, {Jeffrey J.} and Darius Balciunas and Saulius Sumanas",

year = "2015",

month = apr,

day = "1",

doi = "10.1161/ATVBAHA.114.304768",

language = "American English",

volume = "35",

journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",

}

TY - JOUR

T1 - Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis

AU - Craig, Michael P.

AU - Grajevskaja, Viktorija

AU - Liao, Hsin-Kai

AU - Balciuniene, Jorune

AU - Ekker, Stephen C.

AU - Park, Joo-Seop

AU - Essner, Jeffrey J.

AU - Balciunas, Darius

AU - Sumanas, Saulius

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Objective; The E26 transformation-specific domain transcription factor Etv2 / Etsrp / ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis. Approach and Results; Zebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b . Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b , but not fli1a , induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites. Conclusions; Our data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.

AB - Objective; The E26 transformation-specific domain transcription factor Etv2 / Etsrp / ER71 is a master regulator of vascular endothelial differentiation during vasculogenesis, although its later role in sprouting angiogenesis remains unknown. Here, we investigated in the zebrafish model a role for Etv2 and related E26 transformation-specific factors, Fli1a and Fli1b in developmental angiogenesis. Approach and Results; Zebrafish fli1a and fli1b mutants were obtained using transposon-mediated gene trap approach. Individual fli1a and fli1b homozygous mutant embryos display normal vascular patterning, yet the angiogenic recovery observed in older etv2 mutant embryos does not occur in embryos lacking both etv2 and fli1b . Etv2 and fli1b double-deficient embryos fail to form any angiogenic sprouts and show greatly increased apoptosis throughout the axial vasculature. In contrast, fli1a mutation did not affect the recovery of etv2 mutant phenotype. Overexpression analyses indicate that both etv2 and fli1b , but not fli1a , induce the expression of multiple vascular markers and of each other. Temporal inhibition of Etv2 function using photoactivatable morpholinos indicates that the function of Etv2 and Fli1b during angiogenesis is independent from the early requirement of Etv2 during vasculogenesis. RNA-Seq analysis and chromatin immunoprecipitation suggest that Etv2 and Fli1b share the same transcriptional targets and bind to the same E26 transformation-specific sites. Conclusions; Our data argue that there are 2 phases of early vascular development with distinct requirements of E26 transformation-specific transcription factors. Etv2 alone is required for early vasculogenesis, whereas Etv2 and Fli1b function redundantly during late vasculogenesis and early embryonic angiogenesis.

KW - angiogenesis

KW - ETS transcription factor

KW - vasculogenesis

KW - zebrafish

UR - https://corescholar.libraries.wright.edu/bmb/32

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4427907/

U2 - 10.1161/ATVBAHA.114.304768

DO - 10.1161/ATVBAHA.114.304768

M3 - Article

C2 - 25722433

VL - 35

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

ER -

Etv2 and Fli1b Function Together as Key Regulators of Vasculogenesis and Angiogenesis

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