Disruption ofacvrl1increases endothelial cell number in zebrafish cranial vessels

Abstract

The zebrafish mutant violet beauregarde (vbg) can be identified at two days post-fertilization by an abnormal circulation pattern in which most blood cells flow through a limited number of dilated cranial vessels and fail to perfuse the trunk and tail. This phenotype cannot be explained by caudal vessel abnormalities or by a defect in cranial vessel patterning, but instead stems from an increase in endothelial cell number in specific cranial vessels. We show that vbg encodes activin receptor-like kinase 1 (Acvrl1; also known as Alk1), a TGFβ type I receptor that is expressed predominantly in the endothelium of the vessels that become dilated in vbg mutants. Thus, vbg provides a model for the human autosomal dominant disorder, hereditary hemorrhagic telangiectasia type 2, in which disruption of ACVRL1 causes vessel malformations that may result in hemorrhage or stroke.Movies available on-line

Noncanonical protease-activated receptor 1 regulates lymphatic differentiation in zebrafish

“…( Proulx et al., 2010 )), Tg(fli1a:nEGFP) y7 (ref. ( Roman et al., 2002 )), Tg(kdrl:mCherry) (ref. ( Proulx et al., 2010 )), and Tg(lyve1b:TopazYFP) tsu (ref.…”

The versatility and paradox of BMP signaling in endothelial cell behaviors and blood vessel function

“…↓ weight and hemoglobin levels, ↑ hemorrhage and anemia, enlarged heart, dilated pulmonary arteries and veins, AVMs in gastrointestinal tract, uterus, and wounded skin [ 184 , 219 ] Zebrafish embryo (mutant alk1 y6 ): Dilated high-flow cranial AVMs, ↑ number of endothelial cells in cranial vessels due to directed arterial EC migration [ 193 ]. Edema in head, pericardium, and yolk sac [ 194 ] Zebrafish embryo (morpholino alk1 ): Cerebral AVMs by 24 hpf, high-output heart failure by 3–4 dpf [ 196 ] **Embryo (Alk1-Cre-L1, pulmonary EC): Lethal (E17.5); AVMs and dilated/tortuous vitelline arteries in E16.5 extraembryonic vasculature, and AVMs in E17.5 lung vasculature [ 239 ] **Neonate (Alk1-Cre-L1, pulmonary EC): Lethal (P5); Dilated, disorganized, tortuous blood vessels causing hemorrhage in brain/lung/small intestine. AVM shunts in brain and lungs [ 219 ] Neonate (Cdh5-CreERT2): Lethal ≤ 48 h following excision.…”

Arteriovenous Malformations—Current Understanding of the Pathogenesis with Implications for Treatment

“…ENG or ALK1 have also been successfully deleted in zebrafish, in which the endothelium can easily be visualized using fluorescent proteins [80][81][82]. Zebrafish models of cerebral AVMs are particularly useful because their entire cranial circulation can be seen in vivo, and systemic hemodynamic responses occurring in humans are mimicked, such as high output cardiac failure [82].…”