Cytokinetic studies on the aortic endothelium and limb bud vascularization in avian embryos

Seifert, Roswitha; Zhao, Bin; Christ, Bodo

doi:10.1007/bf00186983

Cited by 29 publications

(15 citation statements)

References 25 publications

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“…The transformation of mesenchymal cells to vasoformative ones has been described in embryonic tissues (FUJIMOTO et al, 1987;HARA et al, 1994), in wound healing tissues (MORI et al, 1992;HIRATA et al, 1994) and in tumors (HAMMERSEN et al, 1985). The capillary ingrowth arising from the marginal veins in a manner suggestive of vasculogenesis is considered to be an initial event in the neocapillarization of the avascular zone in our samples since we did not encounter any mitotic figures of endothelial cells of the pre-existing vessels, and we agree with the reports by SEIFERT et al (1992) and BRAND-SABERI et al (1995) that the neocapillarization by transformation of mesenchymal cells to endothelial ones is more prevalent in the avascular zone, while that in the manner of sprouts from the pre-existing vessel frequently occurs beneath the avascular zone in the chick wing bud.…”

Section: Discussionsupporting

confidence: 92%

The Roles of the Marginal Veins in the Differentiation of the Rat Hind Limb Bud: An Immunocytochemical Study.

Kanazawa

Doi

Furukawa

et al. 1996

Archives of Histology and Cytology

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Section: Discussionsupporting

confidence: 92%

The Roles of the Marginal Veins in the Differentiation of the Rat Hind Limb Bud: An Immunocytochemical Study.

Kanazawa

Doi

Furukawa

et al. 1996

Archives of Histology and Cytology

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“…For QH-1 antibody-reaction and BrdUIanti-BrdUtechnique (Seifert et al, 1992) quail embryos of stages 18 to 25 HH were used. The embryos of the appropriate stages were incubated in ovo with 20 pl of a 40 mM BrdU-solution (5-bromo-2'-deoxyuridine, Sigma) for 1 hr.…”

Section: Morphological and Proliferation Studies On Semithin Sectionsmentioning

confidence: 99%

Blood vessel formation in the avian limb bud involves angioblastic and angiotrophic growth

Brand‐Saberi

Seifert

Grim³

et al. 1995

Developmental Dynamics

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The vasculature of the avian limb bud takes its origin from the intersomitic vessels as can be shown by ink perfusion of the embryo. While the primitive vessels form a central network in the early limb bud, an area of about 100 p m in width from the ectoderm inward remains free from lumenized vessels. However, this subectodermal avascular zone contains isolated angioblasts, which can be demonstrated by confocal laser scanning microscopy in connection with QH-1-staining. QH-1-positive cells from the avascular zone are capable of giving rise to endothelial cells when grafted ectopically into a "permissive" environment such as the dorso-lateral paraxial mesoderm. Several grafting sites are compared regarding their permissiveness for capillary formation. In order to investigate the origin of the QH-1-positive angioblasts we carried out injections of DiI-Ac-LDL, which is specifically taken up by endothelial cells and macrophages, and found the lumenized vessels and a few isolated cells in the peripheral limb mesoderm stained. In double-labelling studies combining DiI-Ac-LDL and QH-1, it can be shown that there exists a pool of isolated angioblasts that are only QH-l-positive, but have not incorporated DiI-Ac-LDL. In contrast to the lumenized vessels in the core of the limb bud, we found that angioblasts in the avascular zone do not proliferate, as shown by proliferation studies applying the BrdU-method to semithin sections in connection with QH-l-labelled parallel sections. We conclude that the vascularization of the avian limb bud is achieved by a combination of angiotrophic growth (sprouting of vessels) and angioblastic growth (recruitment of angioblasts from the limb mesoderm).0 1995 Wiley-Liss, Inc.

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“…The limb bud is unique in requiring a complex interaction of both angiogenesis and vasculogenesis during development (8). Vasculogenesis is the formation of a capillary bed from endothelial cells that have differentiated from mesenchymal precursors.…”

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confidence: 99%

Thalidomide is an inhibitor of angiogenesis.

D’Amato

Loughnan

Flynn

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

2,203

1,013

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Thalidomide is a potent teratogen causing dysmelia (stunted limb growth) in humans. We have demonstrated that orally administered thalidomide is an inhibitor of aniogenesis induced by basic fibroblast growth factor in a rabbit cornea micropocket assay. Experiments including the analysis of thalidomide analogs revealed that the antaniogenic activity correlated with the teratogenicity but not with the sedative or the mild immunosuppressive properties of thalidomide. Electron microscopic examination of the corneal neovascularization ofthafidomide-treated rabbits revealed specific ultrastructural changes similar to those seen in the deformed limb bud vasculature of thalidomide-treated embryos. These experiments shed light on the mechanism of thalidomide's teratogenicity and hold promise for the potential use of thalidomide as an orally adminsered drug for the treatment of many diverse dease dependent on angiogenesis.Thalidomide is a potent teratogen. It was developed by Chemie Grunenthal in the 1950s as a sedative that appeared so nontoxic in rodent models that a LD50 could not be established. In 1961, McBride (1) and Lenz (2) described the association between limb defects in babies and maternal thalidomide usage. Although humans are exquisitely sensitive to the teratogenic effects of thalidomide, experiments in rodents failed to reveal similar effects (3, 4). Teratogenic effects could be experimentally reproduced by the administration of thalidomide to pregnant rabbits at an oral dose of 100-300 mg per kg per day (5, 6). Over the past 30 years, the mechanism of thalidomide's teratogenicity has been extensively studied but has remained unsolved (7).We now postulate that the limb defects seen with thalidomide were secondary to an inhibition of blood vessel growth in the developing fetal limb bud. The limb bud is unique in requiring a complex interaction of both angiogenesis and vasculogenesis during development (8). Vasculogenesis is the formation of a capillary bed from endothelial cells that have differentiated from mesenchymal precursors. Angiogenesis is the formation of new blood vessels from sprouts ofpreexisting vessels. Therefore, the limb bud would be a particularly vulnerable target to a teratogen that inhibited endothelial cell function. We chose to examine the effect of thalidomide on growing vasculature in the chicken chorioallantoic membrane and in the rabbit cornea. MATERIALS AND METHODSChicken chorioallantoic membrane (CAM) assays were performed as described (9, 10) and the effects on the developing vasculature were recorded at 48 h after implantation of the 0.5% carboxymethylcellulose pellet containing various drugs. Corneal

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Cytokinetic studies on the aortic endothelium and limb bud vascularization in avian embryos

Cited by 29 publications

References 25 publications

The Roles of the Marginal Veins in the Differentiation of the Rat Hind Limb Bud: An Immunocytochemical Study.

The Roles of the Marginal Veins in the Differentiation of the Rat Hind Limb Bud: An Immunocytochemical Study.

Blood vessel formation in the avian limb bud involves angioblastic and angiotrophic growth

Thalidomide is an inhibitor of angiogenesis.

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