Endoglin expression in early development is associated with vasculogenesis and angiogenesis

Jonker, Leon; Arthur, Helen M.

doi:10.1016/s0925-4773(01)00562-7

Cited by 90 publications

(73 citation statements)

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“…The occurrence of arteriovenous malformations in HHT patients and high endoglin expression in normal developing heart valves pointed to other roles for endoglin in cardiovascular development [1]. This was confirmed in the endoglin knockout mouse, in which we, and others, showed that lack of endoglin expression causes failure of angiogenesis, best seen in the yolk sac, as well as defects in endocardial cushion formation [2][3][4].…”

Section: Referencesmentioning

confidence: 53%

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Abstracts of papers presented at the thirteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 27 and 28 November 2002

Copp

Fisher

2003

Genet. Res.

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Fluorescent in situ hybridization (FISH) has been used to study chromosomes in human preimplantation embryos and high levels of chromosomal mosaicism have been detected. Mosaicism could arise through several mechanisms including abnormal cell divisions (mitotic non-disjunction or anaphase lag), failure of cytokinesis or endoreduplication. The FISH procedure has been criticized as it is prone to failure. In this study a two-probe per chromosome FISH procedure was developed to investigate mosaicism and ensure high FISH efficiency. Three-colour FISH was performed in three rounds. In the first and second rounds different probes were used for chromosomes 1, 11 and 18. In the third round probes were used for chromosomes X, Y and 18. Two groups of embryos were studied on day 5 of development : embryos grown in cleavage medium and embryos grown in blastocyst medium. Fourteen embryos were examined in cleavage medium and 13 were mosaic. To date five embryos have been examined in blastocyst medium and all were mosaic. In 95% of cases results were consistent for each chromosome in the different rounds of hybridization. The type of mosaicism in most cases was diploid/aneuploid mosaics. Chromosome loss was the predominant mechanism, followed by chromosome gain, with few examples of mitotic non-disjunction. Human oocytes and embryos commonly have missing or extra chromosomes (aneuploidy). Many of these embryos fail to develop, implant and reach term. However, 0 . 3% of newborns have a chromosomal abnormality, making aneuploidy the leading genetic cause of physical and mental disability. It is generally assumed that aneuploidy arises solely following resumption of meiosis, during anaphase I and II, and that oocytes arrested in prophase I of meiosis in the primordial pool are chromosomally normal. We have used fluorescence in situ hybridization (FISH) to test the hypothesis that immature primary oocytes are chromosomally normal (diploid) and that no errors arose during earlier germ cell mitosis during fetal life. Primordial and primary follicles were isolated enzymatically and mechanically from ovarian biopsies taken, with informed consent, from women undergoing surgery. Oocytes were dissected from the follicles and spread on microscope slides. Using FISH, 457 oocytes from 37 patients were analysed for aneuploidy of chromosomes 13, 21 and X (chromosomes implicated in early embryonic loss and miscarriage). Rather than the expected two signals, 11 % of analysed oocytes had three signals for one or more chromosomes. Six per cent, 4 % and 2 % of the oocytes had three signals for chromosome 21, X and 13, respectively. The extra signals could represent either trisomy (which would have arisen during germ cell mitosis) or prematurely separated sister chromatids. Either interpretation would predispose the oocyte to further aneuploidy following resumption of meiosis I. Constitutional aneuploidy occurs in at least 5 % of recognized pregnancies, with apparent preferential involvement of the X chromosome and the smaller autosomes. Molecular ...

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Section: Referencesmentioning

confidence: 53%

“…We have shown Igf-2 inhibits MD skeletal muscle apoptosis and stabilizes dystrophic phenotype [1,2]. Igf-2 may thus be suitable for therapeutic use in MD, delivered directly to skeletal muscles.…”

Section: Trophoblast Stem Cells: An In Vitro Model For Imprinted X Inmentioning

confidence: 91%

Abstracts of papers presented at the thirteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 27 and 28 November 2002

Copp

Fisher

2003

Genet. Res.

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“…30,35 In the sinusoidal EC of the liver, Eng expression was strong, whereas Alk1 expression was undetectable. 11,38 In addition, the arterial-EC-predominant expression of Eng was not as apparent as that of Alk1. 38 The data presented in this paper provide useful information for utilizing Alk1-lacZ reporter lines and Alk1-null embryos in the investigation of placental vascular development as well as of pathogenetic mechanisms for HHT and preeclampsia.…”

Section: Alk1 In Placental Vascular Developmentmentioning

confidence: 98%

Activin receptor-like kinase 1 is essential for placental vascular development in mice

Hong

Seki

2007

Laboratory Investigation

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Activin receptor-like kinase 1 (ALK1) is involved in the pathogenesis of hereditary hemorrhagic telangiectasia type II (HHT2) and pulmonary arterial hypertension. We have previously shown that Alk1 is predominantly expressed in the arterial endothelium and plays a pivotal role in the formation of embryonic blood vessels. At present, however, little is known about the precise expression pattern and function of ALK1 during extra-embryonic vascular development. Using previously generated lacZ reporter lines, we sought to examine the expression pattern and role of Alk1 during placental development in mice. Alk1 expression was restricted to endothelial cells of fetal vessels from the emergence of chorioallantoic fusion to the late gestational period, and no detectable Alk1 expression was observed in syncytiotrophoblasts or spongiotrophoblasts. Predominant arterial expression was observed in the umbilical and fetal placental vessels as well as in embryonic vessels. Morphological analysis of Alk1-null embryos indicates that Alk1 is essential for the development of distinct umbilical arteries and veins. The invasion of chorioallantoic mesoderm into the forming labyrinth layer was largely unaffected in the Alk1-null placenta, but chorioallantoic vessels appeared to be severely dilated and fused. Results from this study provide valuable information regarding the role of ALK1 in the development of placental vasculature as well as insights into the pathogenesis of HHT. Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder occurring in one out of 10 000 people. 1,2 The most common clinical symptoms of HHT are nosebleeds and mucocutaneous telangiectases. Telangiectasic lesions exhibit dilation of the vascular lumen, thinning of the vascular wall, and arteriovenous malformations (AVMs)-direct connections between arterioles and venules without intervening capillaries. Large AVMs in the lungs, brain, liver, and gastrointestinal track of HHT patients can cause life-threatening complications. Genetic studies have revealed that heterozygous mutations in ENDOGLIN (ENG) or Activin receptor-like kinase 1 (ALK1; ACVRL1) cause HHT1 and HHT2, respectively. 3,4 Recent reports have shown that some SMAD4 mutations can also cause HHT. 5 ENG and ALK1 are, respectively, a type III and type I receptor for transforming growth factor-b (TGF-b) superfamily ligands. SMAD4 is a common mediator of all SMADdependent TGF-b family signaling. It is conceivable that HHT is caused by impairment of mediating a TGF-b family ligand common to ENG, ALK1, and SMAD4. Although TGFb1 and b3 have been considered the most likely ligands for ENG/ALK1 signaling, as both ENG and ALK1 interact with multiple TGF-b family ligands, the issue concerning the identity of the HHT-causing ligand for ENG/ALK1 remains unresolved. 6 Heterozygous Alk1-null mice develop an array of HHT-like vascular malformations. 7 As the frequency, time of onset, and location of vascular lesions in these mice are as unpredictable as in humans with HHT, the heterozyg...

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“…During development, ENG and ALK1 present very similar expression patterns in areas of vasculogenesis (yolk sac, early embryonic vasculature) and angiogenesis (throughout the late embryonic vascular endothelium) (Jonker and Arthur, 2002;Roelen et al, 1997;Seki et al, 2003). ENG is detected in veins, liver sinusoidal endothelial cells and arteries, while ALK1 is only detected in developing arteries, suggesting a role in arterial differentiation (Jonker and Arthur, 2002;Seki et al, 2003).…”

Section: Normal and Tumor Endothelial Expression Of Eng And Alk1mentioning

confidence: 99%

Beyond VEGF: The NOTCH and ALK1 Signaling Pathways as Tumor Angiogenesis Targets

Nolan-Stevaux¹,

Jun²

2012

Tumor Angiogenesis

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Endoglin expression in early development is associated with vasculogenesis and angiogenesis

Cited by 90 publications

References 13 publications

Abstracts of papers presented at the thirteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 27 and 28 November 2002

Abstracts of papers presented at the thirteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 27 and 28 November 2002

Activin receptor-like kinase 1 is essential for placental vascular development in mice

Beyond VEGF: The NOTCH and ALK1 Signaling Pathways as Tumor Angiogenesis Targets

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