How Does the Ureteric Bud Branch?

Many genes that modulate kidney development have been identified; however, the molecular interactions that direct arborization of the ureteric bud (UB) remain incompletely understood. This article discusses how "systems" approaches may shed light on the structure of the gene network during...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2009-07, Vol.20 (7), p.1465-1469
Main Authors: NIGAM, Sanjay K, SHAH, Mita M
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Communication - physiology
Cell Differentiation - physiology
Epithelial Cells - cytology
Epithelial Cells - physiology
Humans
Kidney - cytology
Kidney - embryology
Kidney - physiology
Medical sciences
Mesoderm - cytology
Mesoderm - physiology
Models, Animal
Morphogenesis - genetics
Morphogenesis - physiology
Nephrology. Urinary tract diseases
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Summary:Many genes that modulate kidney development have been identified; however, the molecular interactions that direct arborization of the ureteric bud (UB) remain incompletely understood. This article discusses how "systems" approaches may shed light on the structure of the gene network during UB branching morphogenesis and the mechanisms involved in the formation of a branched collecting system from a straight epithelial tube in the context of a stage model. In vitro and genetic studies suggest that the stages seem to be governed by a conserved network of genes that establish a "tip-stalk generator"; these genes sustain iterative UB branching tubulogenesis through minimal alterations in the network architecture as a budding system shifts to one that autocatalytically branches through budding. The differential expression of stage-specific positive and inhibitory factors in the mesenchyme, likely presented in the context of heparan sulfate proteoglycans, and effector molecules in the epithelium seems to regulate advancement between stages; similar principles may apply to other branching epithelia such as the lung, salivary gland, pancreas, mammary gland, and prostate. Active mesenchymal interactions with the UB seem to govern vectorial arborization and tapering of the collecting system and its terminal differentiation. Cessation of branching correlates with induction of mesenchyme as well as local extracellular matrix changes. Perturbations of these mechanisms and/or single-nucleotide polymorphisms in genes regulating UB branching may predispose to a variety of renal diseases (e.g., hypertension and chronic kidney disease) by altering nephron number. Decentralization of the gene-protein interaction network may explain the relative paucity of branching phenotypes in mutant mice and in human disease.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2008020132