イシイ　ヤスオ   Ishii Yasuo   石井　泰雄    所属   医学部 医学科    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	An anteroposterior wave of vascular inhibitor downregulation signals aortae fusion along the embryonic midline axis.
掲載誌名	正式名：Development (Cambridge, England) 略　 称：Development ISSNコード：(1477-9129)0950-1991(Linking)
掲載区分	国外
巻・号・頁	137(21),pp.3697-706
著者・共著者	Garriock Robert J, Czeisler Catherine, Ishii Yasuo, Navetta Alicia M, Mikawa Takashi
発行年月	2010/11
概要	Paracrine signals, both positive and negative, regulate the positioning and remodeling of embryonic blood vessels. In the embryos of mammals and birds, the first major remodeling event is the fusion of bilateral dorsal aortae at the midline to form the dorsal aorta. Although the original bilaterality of the dorsal aortae occurs as the result of inhibitory factors (antagonists of BMP signaling) secreted from the midline by the notochord, it is unknown how fusion is later signaled. Here, we report that dorsal aortae fusion is tightly regulated by a change in signaling by the notochord along the anteroposterior axis. During aortae fusion, the notochord ceases to exert its negative influence on vessel formation. This is achieved by a transcriptional downregulation of negative regulators while positive regulators are maintained at pre-fusion levels. In particular, Chordin, the most abundant BMP antagonist expressed in the notochord prior to fusion, undergoes a dramatic downregulation in an anterior to posterior wave. With inhibitory signals diminished and sustained expression of the positive factors SHH and VEGF at the midline, fusion of the dorsal aortae is signaled. These results demonstrate a novel mechanism by which major modifications of the vascular pattern can occur through modulation of vascular inhibitors without changes in the levels of positive vascular regulators.
DOI	10.1242/dev.051664
PMID	20940228