Vessel patterning in the embryo of the zebrafish: guidance by notochord.
We have cloned the zebrafish homolog of the receptor tyrosine kinase flk-1 to provide us with a tool to study normal vascular pattern formation in the developing zebrafish embryo and to compare it to mutants in which vascular pattern is perturbed. We find that during normal development the first angioblasts arise laterally in the mesoderm and then migrate medially to form the primordia of the large axial vessels, the dorsal aorta (axial artery) and the axial vein. Lumen formation occurs shortly before onset of circulation at 24 hr postfertilization. We examined the specification of vascular progenitors in the mutant cloche, which fails to form both vessels and blood. cloche lacks all flk-expressing cells and therefore appears to lack angioblasts. The axial vessels of the trunk form in close proximity to notochord and endoderm, which may provide cues for their formation. The dorsal aorta is normally just ventral to the notochord; the axial vein is just below the dorsal aorta and above the endoderm. floating head (flh) and no tail (ntl) mutants both have defects in the formation of notochord. Both are cell-autonomous lesions, flh abolishing notochord and ntl preventing its differentiation. In both mutants the dorsal aorta fails to form, while formation of the axial vein is less affected. Mosaic analysis of mutant embryos shows that transplanted wild-type cells can become notochord in mutant flh embryos. In these mosaic embryos flh cells expressing flk assemble at the midline, beneath the wild-type notochord, and form an aortic primordium. This suggests that signals from the notochord may guide angioblasts in the fashioning of the dorsal aorta. The notochord seems to be less important for the formation of the vein.
Fouquet
B
B
Cardiovascular Research Center, Massachusetts General Hospital, Charlestown 02129, USA.
Weinstein
B M
BM
Serluca
F C
FC
Fishman
M C
MC
D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000196:embryology; D019521:Body Patterning / Q000502:physiology*; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D008969:Molecular Sequence Data; D009030:Mosaicism; D009154:Mutation; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009672:Notochord / Q000196:embryology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D019170:Somites / Q000737:chemistry; D014680:Veins / Q000196:embryology; D015027:Zebrafish
D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor