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Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase.
Bullock SL
,
Fletcher JM
,
Beddington RS
,
Wilson VA
.
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Heparan sulfate proteoglycans have been implicated in the presentation of a number of secreted signaling molecules to their signal-transducing receptors. We have characterized a gene trap mutation in the gene encoding a heparan sulfate biosynthetic enzyme, heparan sulfate 2-sulfotransferase (HS2ST). Transgenic mice were generated from embryonic stem cells harboring this insertion. lacZ reporter gene activity in heterozygous embryos demonstrates that the gene is expressed differentially during embryogenesis, presumably directing dynamic changes in heparan sulfate structure. Moreover, mice homozygous for the Hs2st gene trap allele die in the neonatal period, exhibiting bilateral renal agenesis and defects of the eye and the skeleton. Analysis of kidney development in Hs2st mutants reveals that the gene is not required for two early events-ureteric bud outgrowth from the Wolffian duct and initial induction of Pax-2 expression in the metanephric mesenchyme. It is required, however, for mesenchymal condensation around the ureteric bud and initiation of branching morphogenesis. Because 2-O-sulfation has been shown to influence the functional interactions of ligands with heparan sulfate in vitro, we discuss the possibility that the Hs2st mutant phenotype is a consequence of compromised interactions between growth factors and their signal-transducing receptors. These data provide the first genetic evidence that the regulated synthesis of differentially glycosylated proteoglycans can affect morphogenesis during vertebrate development.
Altschul,
Basic local alignment search tool.
1990, Pubmed
Altschul,
Basic local alignment search tool.
1990,
Pubmed
Bai,
Turnover of heparan sulfate depends on 2-O-sulfation of uronic acids.
1997,
Pubmed
Bai,
An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation.
1996,
Pubmed
Beddington,
An in situ transgenic enzyme marker for the midgestation mouse embryo and the visualization of inner cell mass clones during early organogenesis.
1989,
Pubmed
Bernfield,
Biology of the syndecans: a family of transmembrane heparan sulfate proteoglycans.
1992,
Pubmed
Binari,
Genetic evidence that heparin-like glycosaminoglycans are involved in wingless signaling.
1997,
Pubmed
Chintala,
Role of heparan sulfate in the terminal differentiation of growth plate chondrocytes.
1995,
Pubmed
Cho,
Molecular nature of Spemann's organizer: the role of the Xenopus homeobox gene goosecoid.
1991,
Pubmed
,
Xenbase
Chomczynski,
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
1987,
Pubmed
Davies,
Sulphated proteoglycan is required for collecting duct growth and branching but not nephron formation during kidney development.
1995,
Pubmed
DeBry,
Human/mouse homology relationships.
1996,
Pubmed
Dressler,
Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.
1990,
Pubmed
Dressler,
Pax-2 is a DNA-binding protein expressed in embryonic kidney and Wilms tumor.
1992,
Pubmed
Dudley,
A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye.
1995,
Pubmed
Durbec,
GDNF signalling through the Ret receptor tyrosine kinase.
1996,
Pubmed
,
Xenbase
Fahrner,
Transcription of H-2 and Qa genes in embryonic and adult mice.
1987,
Pubmed
Fantes,
A high-resolution integrated physical, cytogenetic, and genetic map of human chromosome 11: distal p13 to proximal p15.1.
1995,
Pubmed
Finch,
Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions.
1995,
Pubmed
Gallagher,
Structure and function of heparan sulphate proteoglycans.
1986,
Pubmed
GROBSTEIN,
Inductive epitheliomesenchymal interaction in cultured organ rudiments of the mouse.
1953,
Pubmed
Gyapay,
A radiation hybrid map of the human genome.
1996,
Pubmed
Häcker,
The Drosophila sugarless gene modulates Wingless signaling and encodes an enzyme involved in polysaccharide biosynthesis.
1997,
Pubmed
Haerry,
Defects in glucuronate biosynthesis disrupt Wingless signaling in Drosophila.
1997,
Pubmed
Harrison,
Isolation of novel tissue-specific genes from cDNA libraries representing the individual tissue constituents of the gastrulating mouse embryo.
1995,
Pubmed
Hashimoto,
Molecular cloning and expression of rat liver N-heparan sulfate sulfotransferase.
1992,
Pubmed
Herzlinger,
Induction of kidney epithelial morphogenesis by cells expressing Wnt-1.
1994,
Pubmed
Kato,
Cell surface syndecan-1 on distinct cell types differs in fine structure and ligand binding of its heparan sulfate chains.
1994,
Pubmed
Kent,
A male-specific role for SOX9 in vertebrate sex determination.
1996,
Pubmed
Kessel,
Homeotic transformations of murine vertebrae and concomitant alteration of Hox codes induced by retinoic acid.
1991,
Pubmed
Kispert,
Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips.
1996,
Pubmed
Kispert,
Immunohistochemical analysis of the Brachyury protein in wild-type and mutant mouse embryos.
1994,
Pubmed
,
Xenbase
Klagsbrun,
A dual receptor system is required for basic fibroblast growth factor activity.
1991,
Pubmed
Klever,
Chromosomal in situ suppression hybridization after Giemsa banding.
1991,
Pubmed
Kobayashi,
Molecular cloning and expression of Chinese hamster ovary cell heparan-sulfate 2-sulfotransferase.
1997,
Pubmed
Kobayashi,
Purification and characterization of heparan sulfate 2-sulfotransferase from cultured Chinese hamster ovary cells.
1996,
Pubmed
Kreidberg,
WT-1 is required for early kidney development.
1993,
Pubmed
Lee,
Autoproteolysis in hedgehog protein biogenesis.
1994,
Pubmed
Leppä,
Syndecan expression regulates cell morphology and growth of mouse mammary epithelial tumor cells.
1992,
Pubmed
Luo,
BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning.
1995,
Pubmed
Lyon,
Interaction of hepatocyte growth factor with heparan sulfate. Elucidation of the major heparan sulfate structural determinants.
1994,
Pubmed
Maccarana,
Minimal sequence in heparin/heparan sulfate required for binding of basic fibroblast growth factor.
1993,
Pubmed
Miyamoto,
Defects of urogenital development in mice lacking Emx2.
1997,
Pubmed
Moore,
Renal and neuronal abnormalities in mice lacking GDNF.
1996,
Pubmed
Morais da Silva,
Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds.
1996,
Pubmed
Nehls,
Two large insert vectors, lambda PS and lambda KO, facilitate rapid mapping and targeted disruption of mammalian genes.
1994,
Pubmed
Nurcombe,
Developmental regulation of neural response to FGF-1 and FGF-2 by heparan sulfate proteoglycan.
1993,
Pubmed
Perantoni,
Basic fibroblast growth factor can mediate the early inductive events in renal development.
1995,
Pubmed
Pichel,
Defects in enteric innervation and kidney development in mice lacking GDNF.
1996,
Pubmed
Powers,
On the components of segregation distortion in Drosophila melanogaster. V. Molecular analysis of the Sd locus.
1991,
Pubmed
Rapraeger,
Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation.
1991,
Pubmed
Reichsman,
Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction.
1996,
Pubmed
Ruppert,
Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity.
1996,
Pubmed
Saksela,
Release of basic fibroblast growth factor-heparan sulfate complexes from endothelial cells by plasminogen activator-mediated proteolytic activity.
1990,
Pubmed
Sánchez,
Renal agenesis and the absence of enteric neurons in mice lacking GDNF.
1996,
Pubmed
Schlessinger,
Regulation of growth factor activation by proteoglycans: what is the role of the low affinity receptors?
1995,
Pubmed
Schuchardt,
Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development.
1996,
Pubmed
Schuchardt,
Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret.
1994,
Pubmed
Skarnes,
Capturing genes encoding membrane and secreted proteins important for mouse development.
1995,
Pubmed
Stark,
Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4.
1994,
Pubmed
Suzuki,
Effects of various growth factors on a chondrocyte differentiation model.
1992,
Pubmed
Torres,
Pax-2 controls multiple steps of urogenital development.
1995,
Pubmed
Trupp,
Functional receptor for GDNF encoded by the c-ret proto-oncogene.
1996,
Pubmed
Turnbull,
Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate.
1992,
Pubmed
Vainio,
Epithelial-mesenchymal interactions regulate the stage-specific expression of a cell surface proteoglycan, syndecan, in the developing kidney.
1989,
Pubmed
Vainio,
Inductive tissue interactions, cell signaling, and the control of kidney organogenesis.
1997,
Pubmed
Vortkamp,
Regulation of rate of cartilage differentiation by Indian hedgehog and PTH-related protein.
1996,
Pubmed
Wlad,
Biosynthesis of heparin. Different molecular forms of O-sulfotransferases.
1994,
Pubmed
Woods,
Syndecan 4 heparan sulfate proteoglycan is a selectively enriched and widespread focal adhesion component.
1994,
Pubmed
Yayon,
Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.
1991,
Pubmed
