Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7

Nichol, Donna; Shawber, Carrie J.; Fitch, Michael J.; Bambino, Kathryn; Sharma, Anshula; Kitajewski, Jan; Stuhlmann, Heidi

doi:10.1182/blood-2010-03-274860

Cited by 91 publications

(145 citation statements)

References 41 publications

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“…Previous studies have shown that Egfl7 modulates Notch signaling in vivo in mouse embryos and in vitro in HUVECs, human trophoblast cells and neural stem cells (Nichol et al, 2010;Massimiani et al, 2015;Schmidt et al, 2009). To examine whether Egfl7 modulates Notch signaling in the developing placental labyrinth, we performed real time RT-PCR for Notch target genes in pre-placental tissues (E8.5) or placentas (E9.5, E12.5) from C57BL/6J control and Egfl7 −/− mice.…”

Section: Syna Expression Was Significantly Decreased In Egfl7mentioning

confidence: 99%

“…Furthermore, egfl7 morphant zebrafish display severe vascular defects, whereas embryos of egfl7 mutant zebrafish and one Egfl7-specific knockout mouse line do not show obvious phenotypes, owing to activation of compensatory genes (Fish et al, 2008;Kuhnert et al, 2008;Nichol and Stuhlmann, 2012;Rossi et al, 2015;Wang et al, 2008). Conversely, endothelial-specific overexpression of Egfl7 in mice results in vascular defects during embryogenesis and pathological vascularization in the neonatal retina (Nichol et al, 2010;Bambino et al, 2014), suggesting a specific role for Egfl7 in vascular development.…”

Section: Introductionmentioning

confidence: 99%

“…Egfl7 has been shown to promote migration of ECs and trophoblast cells (Campagnolo et al, 2005;Massimiani et al, 2015;Nichol et al, 2010). Its expression is downregulated in human pre-eclamptic placentas Junus et al, 2012), placentas of a mouse model of PE prior to the onset of clinical signs , and in plasma of individuals with pregnancies affected by intrauterine growth restriction (Zanello et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Altered feto-placental vascularization, feto-placental malperfusion, and fetal growth restriction in mice with Egfl7 loss-of-function

et al. 2017

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EGFL7 is a secreted angiogenic factor produced by embryonic endothelial cells. To understand its role in placental development, we established a novel Egfl7 knockout mouse. The mutant mice have gross defects in chorioallantoic branching morphogenesis and placental vascular patterning. Microangiography and 3D imaging revealed patchy perfusion of Egfl7 −/− placentas marked by impeded blood conductance through sites of narrowed vessels. Consistent with poor feto-placental perfusion, Egfl7 knockout resulted in reduced placental weight and fetal growth restriction. The placentas also showed abnormal fetal vessel patterning and over 50% reduction in fetal blood space. In vitro, placental endothelial cells were deficient in migration, cord formation and sprouting. Expression of genes involved in branching morphogenesis, Gcm1, Syna and Synb, and in patterning of the extracellular matrix, Mmrn1, were temporally dysregulated in the placentas. Egfl7 knockout did not affect expression of the microRNA embedded within intron 7. Collectively, these data reveal that Egfl7 is crucial for placental vascularization and embryonic growth, and may provide insight into etiological factors underlying placental pathologies associated with intrauterine growth restriction, which is a significant cause of infant morbidity and mortality.

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Section: Syna Expression Was Significantly Decreased In Egfl7mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Altered feto-placental vascularization, feto-placental malperfusion, and fetal growth restriction in mice with Egfl7 loss-of-function

et al. 2017

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“…EGFL7 is secreted by endothelial cells and is implicated in the regulation of blood vessel formation and cell migration through interaction with receptors of the Notch family (1,(8)(9)(10)(11). EGFL7 binds to the extracellular domains of all four Notch receptor isoforms and inhibits Jagged-induced Notch signaling (12).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization and expression analysis of mouse epidermal growth factor-like domain 8

Song

Ikram

Subhan

et al. 2015

International Journal of Molecular Medicine

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Abstract. Epidermal growth factor (EGF)-like (EGFL)domain, a common structural module in numerous secreted or transmembrane proteins, is generally involved in protein-protein interactions. To date, several EGFL proteins have been identified and characterized, but little is known about EGFL domain 8 (EGFL8). The present study reported the molecular characterization and expression analysis of EGFL8 in mice. Mouse EGFL8 amplified using a reverse transcription-polymerase chain reaction approach was sequenced and characterized. Mouse EGFL8 encodes a protein of 293 amino acids with two EGFL domains, an Emilin-like domain and a Ca 2+ -binding EGFL domain, which has a molecular mass of 32 kDa. The coding sequence has a high degree of amino acid sequence identity across species, and the EGFL domain has been highly conserved in various species during evolutionary radiation. A phylogenetic tree calculated using the neighbor-joining method revealed that EGFL8 and EGFL7 are more closely associated with each other than either is to EGFL3, and they cluster with EGFL6. It was found that mouse EGFL8 protein was highly expressed in diverse mouse tissue types, including the thymus, lymph nodes, testis, ovaries, epididymis, ductus deferens, ileum, colon, stomach, esophagus, lung, uterus, urinary bladder, skin, spleen, adrenal glands and penis. These results are of great use in understanding the biological roles of mouse EGFL8 for further study.

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“…48 EGFL7 has also been demonstrated to antagonize Notch signaling in endothelial cells as well as neural stem cells. 49,50 Again, however, it remains to be determined if RhoA is a direct or indirect downstream target of this pathway.…”

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confidence: 99%

The CASZ1/Egfl7transcriptional pathway is required for RhoA expression in vascular endothelial cells

2013

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Impaired angiogenesis and altered Notch signaling in mice overexpressing endothelial Egfl7

Cited by 91 publications

References 41 publications

Altered feto-placental vascularization, feto-placental malperfusion, and fetal growth restriction in mice with Egfl7 loss-of-function

Altered feto-placental vascularization, feto-placental malperfusion, and fetal growth restriction in mice with Egfl7 loss-of-function

Molecular characterization and expression analysis of mouse epidermal growth factor-like domain 8

The CASZ1/Egfl7transcriptional pathway is required for RhoA expression in vascular endothelial cells

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