Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos. / Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi; Kim, Jun-Dae; Meadows, Stryder; Fischer, Johanna C; Wang, Yeqi; Cleaver, Ondine; Qyang, Yibing; Ober, Elke A; Jin, Suk-Won.
I: Circulation Research, Bind 114, Nr. 1, 03.01.2014, s. 56-66.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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
VL - 114
SP - 56
EP - 66
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 1
ER -
ID: 128641623