mutation in utp15 disrupts vascular patterning in a p53-dependent manner in zebrafish embryos突变utp15破坏血管模式在斑马鱼胚胎p53-dependent方式.pdfVIP

Mutation in utp15 Disrupts Vascular Patterning in a p53- Dependent Manner in Zebrafish Embryos 1 1,2,3,4 Kevin Mouillesseaux , Jau-Nian Chen * 1 Department of Molecular, Cell, and Developmental Biology, University of California Los Angeles, Los Angeles, California, United States of America, 2 Molecular Biology Institute, University of California Los Angeles, Los Angeles, California, United States of America, 3 Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, United States of America, 4 Cardiovascular Research Laboratory, University of California Los Angeles, Los Angeles, California, United States of America Abstract Background: Angiogenesis is the process by which the highly branched and functional vasculature arises from the major vessels, providing developing tissues with nutrients, oxygen, and removing metabolic waste. During embryogenesis, vascular patterning is dependent on a tightly regulated balance between pro- and anti-angiogenic signals, and failure of angiogenesis leads to embryonic lethality. Using the zebrafish as a model organism, we sought to identify genes that influence normal vascular patterning. Methodology and Principal Findings: In a forward genetic screen, we identified mutant LA1908, which manifests massive apoptosis during early embryogenesis, abnormal expression of several markers of arterial-venous specification, delayed angiogenic sprouting of the intersegmental vessels (ISV), and malformation of the caudal vein plexus (CVP), indicating a critical role for LA1908 in cell survival and angiogenesis. Genetic mapping and sequencing identified a G to A transition in the splice site preceding exon 11 of utp15 in LA1908 mutant embryos. Overexpression of wild