title: Metalloprotease-dependent onset of blood circulation in zebrafish.
abstract: The primitive blood circulation requires intravascular plasma flow. However, it remains unclear whether the onset of earliest blood circulation is dependent solely on establishment of a functional circulatory organ or whether it also requires active processes inherent in blood cells. In this study, we present novel mechanisms for the onset of blood circulation by monitoring fluorescently labeled blood precursors and blood vessels in zebrafish. The earliest blood circulation occurs synchronously. This synchrony is achieved by the retention of erythroid precursors on the lumen of the vasculature after their invasion from the subaortic region, and then by simultaneous release of these precursors into the flow. Morphological and biochemical analyses suggest that the onset of blood circulation accompanies disruption of blood cell-to-vessel adhesion and requires metalloprotease-dependent processes. ADAM8, a member of the a disintegrin and metalloprotease (ADAM) family, mediates the onset of blood circulation. In ADAM8-depleted embryos, erythroid cells fail to detach from the vascular lumen and stagnate. Expression of a protease-defective ADAM8 in erythroid cells causes dominant-negative effects on blood circulation, suggesting cell-autonomous roles of ADAM8. Based on these findings, we propose that the first erythroid cells require both flow-dependent passive and proteolysis-dependent active processes to enter the circulation.
authors.affiliation: Department of Growth Regulation, Institute for Frontier Medical Sciences, Kyoto University, Kawahara-cho 53, Shogo-in, Kyoto 606-8507, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Iida
authors.forename: Kazuya
authors.initials: K
authors.lastname: Sakaguchi
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Sato
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Sakurai
authors.forename: Daigo
authors.initials: D
authors.lastname: Nishimura
authors.forename: Aya
authors.initials: A
authors.lastname: Iwaki
authors.forename: Miki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Makoto
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Misaki
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kawahara
authors.forename: Atsuko
authors.initials: A
authors.lastname: Sehara-Fujisawa
mesh_terms: D000818:Animals; D001775:Blood Circulation; D045726:Metalloproteases / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D045726:Metalloproteases