Integrin alpha8beta1 is critically important for epithelial-mesenchymal interactions during kidney morphogenesis.
We present genetic evidence that integrins regulate epithelial-mesenchymal interactions during organogenesis. Mice with a mutation in the alpha8 gene do not express the integrin alpha8 beta1 and exhibit profound deficits in kidney morphogenesis. In wild-type animals, inductive interactions between the ureteric epithelium and metanephric mesenchyme are essential for kidney morphogenesis. In alpha8 mutant homozygotes, growth and branching of the ureteric bud and recruitment of mesenchymal cells into epithelial structures are defective. Consistent with these phenotypes, alpha8 expression is induced in mesenchymal cells upon contact with the ureter. Since none of its previously identified ligands appears likely to mediate the essential functions of alpha8 beta1 in kidney morphogenesis, we have used an alpha8 beta1-alkaline phosphatase chimera to localize novel ligand(s) in the growing ureter. The distribution of these ligand(s) makes them strong candidates for regulators of kidney morphogenesis.
Müller
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U
Department of Physiology, University of California, San Francisco 94143, USA.
Wang
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D
Denda
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Meneses
J J
JJ
Pedersen
R A
RA
Reichardt
L F
LF
D000483:Alleles; D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication / Q000235:genetics; D002460:Cell Line / Q000737:chemistry / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D004847:Epithelial Cells; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D016023:Integrins / Q000235:genetics*; D007668:Kidney / Q000166:cytology* / Q000196:embryology* / Q000473:pathology; D008024:Ligands; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009024:Morphogenesis / Q000235:genetics; D051762:PAX2 Transcription Factor; D010641:Phenotype; D020800:Receptor, Nerve Growth Factor; D017469:Receptors, Fibronectin / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics; D014513:Ureter / Q000166:cytology / Q000196:embryology / Q000473:pathology
D004268:DNA-Binding Proteins; D016023:Integrins; D008024:Ligands; D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D020800:Receptor, Nerve Growth Factor; D017469:Receptors, Fibronectin; D017475:Receptors, Nerve Growth Factor; D014157:Transcription Factors; C094866:integrin alpha8beta1