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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.

SUBMITTER: Dunworth WP

PROVIDER: S-EPMC4047637 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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

Dunworth William P WP Cardona-Costa Jose J Bozkulak Esra Cagavi EC Kim Jun-Dae JD Meadows Stryder S Fischer Johanna C JC Wang Yeqi Y Cleaver Ondine O Qyang Yibing Y Ober Elke A EA Jin Suk-Won SW

Circulation research 20131011 1

<h4>Rationale</h4>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.<h4>Objective</h4>Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development.<h4>Methods and results</h4>BMP2 signaling negatively regulates the formation o ...[more]

PMID: 24122719

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Project description:This study investigated the effects of bone morphogenetic protein 6 (BMP6) supplementation in the medium during in vitro maturation (IVM) on the developmental potential of oocytes and in the subsequent development of cloned yak embryos. Cumulus-oocyte complexes (COCs) were aspirated from the antral follicles of yak ovaries and cultured with different concentrations of recombinant human BMP6 in oocyte maturation medium. Following maturation, the metaphase II (MII) oocytes were used for somatic cell nuclear transfer (SCNT), and these were cultured in vitro. The development of blastocysts and cell numbers were detected on day 8. The apoptosis and histone modifications of yak cloned blastocysts were evaluated by detecting the expression of relevant genes and proteins (Bax, Bcl-2, H3K9ac, H3K18ac, and H3K9me3) using relative quantitative RT-PCR or immunofluorescence. The presence of 100 ng/mL BMP6 significantly enhanced the oocyte maturation ratios (66.12 ± 2.04% vs. 73.11 ± 1.38%), cleavage rates (69.40 ± 1.03% vs. 78.16 ± 0.93%), and blastocyst formation rates (20.63 ± 1.32% vs. 28.16 ± 1.67%) of cloned yak embryos. The total blastocysts (85.24 ± 3.12 vs. 103.36 ± 5.28), inner cell mass (ICM) cell numbers (19.59 ± 2.17 vs. 32.20 ± 2.61), and ratio of ICM to trophectoderm (TE) (22.93 ± 1.43% vs. 31.21 ± 1.62%) were also enhanced (p < 0.05). The ratio of the Bax to the Bcl-2 gene was lowest in the SCNT + BMP6 groups (p < 0.05). The H3K9ac and H3K18ac levels were increased in SCNT + BMP6 groups (p < 0.05), whereas the H3K9me3 level was decreased; the differences in blastocysts were not significant (p > 0.05). These study results demonstrate that addition of oocyte maturation medium with recombinant BMP6 enhances yak oocyte developmental potential and the subsequent developmental competence of SCNT embryos, and provides evidence that BMP6 is an important determinant of mammalian oocyte developmental reprogramming.

Dataset Information

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

Publications

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

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