Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-3-13
pubmed:databankReference
pubmed:abstractText
The zebrafish cloche mutation affects both the endothelial and hematopoietic lineages at a very early stage (Stainier, D. Y. R., Weinstein, B. M., Detrich, H. W., Zon, L. I. and Fishman, M. C. (1995). Development 121, 3141-3150). The most striking vascular phenotype is the absence of endocardial cells from the heart. Microscopic examination of mutant embryos reveals the presence of endothelial-like cells in the lower trunk and tail regions while head vessels appear to be missing, indicating a molecular diversification of the endothelial lineage. Cell transplantation experiments show that cloche acts cell-autonomously within the endothelial lineage. To analyze further the role of cloche in regulating endothelial cell differentiation, we have examined the expression of flk-1 and tie, two receptor tyrosine kinase genes expressed early and sequentially in the endothelial lineage. In wild-type fish, flk-1-positive cells are found throughout the embryo and differentiate to form the nascent vasculature. In cloche mutants, flk-1-positive cells are found only in the lower trunk and tail regions, and this expression is delayed as compared to wild-type. Unlike the flk-1-positive cells in wild-type embryos, those in cloche mutants do not go on to express tie, suggesting that their differentiation is halted at an early stage. We also find that the cloche mutation is not linked to flk-1. These data indicate that cloche affects the differentiation of all endothelial cells and that it acts at a very early stage, either by directly regulating flk-1 expression or by controlling the differentiation of cells that normally develop to express flk-1. cloche mutants also have a blood deficit and their hematopoietic tissues show no expression of the hematopoietic transcription factor genes GATA-1 or GATA-2 at early stages. Because the appearance of distinct levels of flk-1 expression is delayed in cloche mutants, we examined GATA-1 expression at late embryonic stages and found some blood cell differentiation that appears to be limited to the region lined by the flk-1-expressing cells. The spatial restriction of blood in the ventroposterior-most region of cloche mutant embryos may be indicative of a ventral source of signal(s) controlling hematopoietic differentiation. In addition, the restricted colocalization of blood and endothelium in cloche mutants suggests that important interactions occur between these two lineages during normal development.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
124
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
381-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9053314-Amino Acid Sequence, pubmed-meshheading:9053314-Animals, pubmed-meshheading:9053314-Base Sequence, pubmed-meshheading:9053314-Cell Differentiation, pubmed-meshheading:9053314-Chromosome Mapping, pubmed-meshheading:9053314-Deoxyribonucleases, Type II Site-Specific, pubmed-meshheading:9053314-Embryo, Nonmammalian, pubmed-meshheading:9053314-Embryonic Induction, pubmed-meshheading:9053314-Endothelium, pubmed-meshheading:9053314-Genetic Linkage, pubmed-meshheading:9053314-Heart, pubmed-meshheading:9053314-Hematopoiesis, pubmed-meshheading:9053314-Hematopoietic Stem Cells, pubmed-meshheading:9053314-Humans, pubmed-meshheading:9053314-Molecular Sequence Data, pubmed-meshheading:9053314-Polymorphism, Restriction Fragment Length, pubmed-meshheading:9053314-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:9053314-Receptors, Growth Factor, pubmed-meshheading:9053314-Receptors, Vascular Endothelial Growth Factor, pubmed-meshheading:9053314-Sequence Homology, Amino Acid, pubmed-meshheading:9053314-Transcription, Genetic, pubmed-meshheading:9053314-Zebrafish
pubmed:year
1997
pubmed:articleTitle
The zebrafish gene cloche acts upstream of a flk-1 homologue to regulate endothelial cell differentiation.
pubmed:affiliation
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0554, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't