Cell-cell interactions driving kidney morphogenesis

Alexander N. Combes, Jamie A. Davies, Melissa H. Little

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Otherpeer-review

37 Citations (Scopus)

Abstract

The mammalian kidney forms via cell-cell interactions between an epithelial outgrowth of the nephric duct and the surrounding nephrogenic mesenchyme. Initial morphogenetic events include ureteric bud branching to form the collecting duct (CD) tree and mesenchymal-to-epithelial transitions to form the nephrons, requiring reciprocal induction between adjacent mesenchyme and epithelial cells. Within the tips of the branching ureteric epithelium, cells respond to mesenchyme-derived trophic factors by proliferation, migration, and mitosis-associated cell dispersal. Self-inhibition signals from one tip to another play a role in branch patterning. The position, survival, and fate of the nephrogenic mesenchyme are regulated by ECM and secreted signals from adjacent tip and stroma. Signals from the ureteric tip promote mesenchyme self-renewal and trigger nephron formation. Subsequent fusion to the CDs, nephron segmentation and maturation, and formation of a patent glomerular basement membrane also require specialized cell-cell interactions. Differential cadherin, laminin, nectin, and integrin expression, as well as intracellular kinesin and actin-mediated regulation of cell shape and adhesion, underlies these cell-cell interactions. Indeed, the capacity for the kidney to form via self-organization has now been established both via the recapitulation of expected morphogenetic interactions after complete dissociation and reassociation of cellular components during development as well as the in vitro formation of 3D kidney organoids from human pluripotent stem cells. As we understand more about how the many cell-cell interactions required for kidney formation operate, this enables the prospect of bioengineering replacement structures based on these self-organizing properties.

Original languageEnglish
Title of host publicationCellular Adhesion in Development and Disease
EditorsAlpha S. Yap
PublisherAcademic Press
Chapter14
Pages467-508
Number of pages42
ISBN (Print)9780124077584
DOIs
Publication statusPublished - 2015
Externally publishedYes

Publication series

NameCurrent Topics in Developmental Biology
Volume112
ISSN (Print)0070-2153

Keywords

  • Cadherin
  • Cap mesenchyme
  • Cell-cell adhesion
  • Glomerular basement membrane
  • Integrin
  • Kidney development
  • Mesenchymal-to-epithelial transition
  • Mitosis-associated cell dispersal
  • Renal vesicle
  • Self-organization

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