Defects in aortic fusion and craniofacial vasculature in the holoprosencephalic mouse embryo under inhibition of sonic hedgehog signaling
Defects in aortic fusion and craniofacial vasculature in the holoprosencephalic mouse embryo under inhibition of sonic hedgehog signaling
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DOI：
10.1097/00001665-200607000-00026
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发表时间：
2006-07-01
影响因子：
0.9
通讯作者：
Yamagishi, Masaaki
中科院分区：
文献类型：
--
作者：
Nagase, Takashi;Nagase, Miki;Yamagishi, Masaaki
声波刺猬（Shh）是众所周知的面部和神经发育中不可缺少的形态发生素，最近它作为一种有效的血管生成因子也受到了广泛的关注。我们之前通过对体外培养的小鼠胚胎施用环杷明（刺猬信号传导的特异性抑制剂）创建了前脑无裂畸形的动物模型，并发现了几种类型的血管生成缺陷。在这项研究中，我们关注同一模型中的其他血管生成表型。当胚胎第 (E) 8.0-9.5 天添加环杷明时，一对未成熟的背主动脉（通常在 E9.5 时融合形成单个主动脉）仍然需要分离。通过阻断Shh信号，主动脉周围血管内皮生长因子和骨形态发生蛋白4（主动脉融合的假定介质）的表达也减少。当E8.5-10.5添加环杷明时，颅面部区域表面的血管（可能是外主静脉）延伸且畸形。这些结果表明，Shh 信号传导对于胚胎血管生成的某些方面至关重要，并且前脑无裂畸形的病理生理学可能至少部分涉及 Shh 依赖性血管生成。
Sonic hedgehog (Shh) is a well-known morphogen indispensable in facial and nervous development, and recently it has also garnered much attention as a potent angiogenic factor. We previously created an animal model of holoprosencephaly by administration of cyclopamine, a specific inhibitor of hedgehog signaling, to the mouse embryos cultured in vitro, and found several types of angiogenic defects. In this study, we focused on other angiogenic phenotypes in the same model. When cyclopamine was added for embryonic day (E) 8.0-9.5, a pair of immature dorsal aortae, which normally fuse to form the single aorta by E9.5, remained to be separated. Expressions of vascular endothelial growth factor and bone morphogenetic protein 4, putative mediators of aortic fusion, were also reduced around the aorta by blockade of Shh signaling. When cyclopamine was added for E8.5-10.5, vessels on the surface of craniofacial region (possibly external cardinal veins) were extended and malformed. These results suggest that Shh signaling is essential for some aspects of embryonic angiogenesis, and that pathophysiology of holoprosencephaly may involve, at least in part, the Shh-dependent angiogenesis.