Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

William P Dunworth; Jose Cardona-Costa; Esra Cagavi Bozkulak; Jun-Dae Kim; Stryder Meadows; Johanna C Fischer; Yeqi Wang; Ondine Cleaver; Yibing Qyang; Elke A Ober; Suk-Won Jin

doi:10.1161/CIRCRESAHA.114.302452

Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

William P Dunworth, Jose Cardona-Costa, Esra Cagavi Bozkulak, Jun-Dae Kim, Stryder Meadows, Johanna C Fischer, Yeqi Wang, Ondine Cleaver, Yibing Qyang, Elke A Ober, Suk-Won Jin

Laboratory

60 Citationer (Scopus)

Abstract

RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown.

OBJECTIVE: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development.

METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development.

CONCLUSIONS: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.

Originalsprog	Engelsk
Tidsskrift	Circulation Research
Vol/bind	114
Udgave nummer	1
Sider (fra-til)	56-66
Antal sider	11
ISSN	0009-7330
DOI	https://doi.org/10.1161/CIRCRESAHA.114.302452
Status	Udgivet - 3 jan. 2014

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10.1161/CIRCRESAHA.114.302452

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@article{355775af3b644446b988601b84abdaea,

title = "Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos",

abstract = "RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown.OBJECTIVE: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development.METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development.CONCLUSIONS: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.",

keywords = "Animals, Bone Morphogenetic Protein 2, Cell Differentiation, Cell Line, Embryoid Bodies, Endothelial Cells, Endothelium, Lymphatic, Gene Expression Regulation, Developmental, Homeodomain Proteins, Humans, Lymphatic Vessels, Mice, MicroRNAs, Signal Transduction, Smad Proteins, Transcription, Genetic, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins",

author = "Dunworth, {William P} and Jose Cardona-Costa and Bozkulak, {Esra Cagavi} and Jun-Dae Kim and Stryder Meadows and Fischer, {Johanna C} and Yeqi Wang and Ondine Cleaver and Yibing Qyang and Ober, {Elke A} and Suk-Won Jin",

year = "2014",

month = jan,

day = "3",

doi = "10.1161/CIRCRESAHA.114.302452",

language = "English",

volume = "114",

pages = "56--66",

journal = "Circulation Research",

issn = "0009-7330",

publisher = "AHA/ASA",

number = "1",

}

TY - JOUR

T1 - Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

AU - Dunworth, William P

AU - Cardona-Costa, Jose

AU - Bozkulak, Esra Cagavi

AU - Kim, Jun-Dae

AU - Meadows, Stryder

AU - Fischer, Johanna C

AU - Wang, Yeqi

AU - Cleaver, Ondine

AU - Qyang, Yibing

AU - Ober, Elke A

AU - Jin, Suk-Won

PY - 2014/1/3

Y1 - 2014/1/3

N2 - RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown.OBJECTIVE: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development.METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development.CONCLUSIONS: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.

AB - RATIONALE: The emergence of lymphatic endothelial cells (LECs) seems to be highly regulated during development. Although several factors that promote the differentiation of LECs in embryonic development have been identified, those that negatively regulate this process are largely unknown.OBJECTIVE: Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development.METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2 signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox protein 1 during development.CONCLUSIONS: Our data identify BMP2 as a key negative regulator for the emergence of the lymphatic lineage during vertebrate development.

KW - Animals

KW - Bone Morphogenetic Protein 2

KW - Cell Differentiation

KW - Cell Line

KW - Embryoid Bodies

KW - Endothelial Cells

KW - Endothelium, Lymphatic

KW - Gene Expression Regulation, Developmental

KW - Homeodomain Proteins

KW - Humans

KW - Lymphatic Vessels

KW - Mice

KW - MicroRNAs

KW - Signal Transduction

KW - Smad Proteins

KW - Transcription, Genetic

KW - Tumor Suppressor Proteins

KW - Zebrafish

KW - Zebrafish Proteins

U2 - 10.1161/CIRCRESAHA.114.302452

DO - 10.1161/CIRCRESAHA.114.302452

M3 - Journal article

C2 - 24122719

SN - 0009-7330

VL - 114

SP - 56

EP - 66

JO - Circulation Research

JF - Circulation Research

IS - 1

ER -

Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

Abstract

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