The direction of gut looping is established by changes in the extracellular matrix and in cell: Cell adhesion

Natasza A. Kurpios, Marta Ibañes, Nicole M. Davis, Wei Lui, Tamar Katz, James F. Martin, Juan Carlos Izpisua Belmonte, Clifford J. Tabin

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

The counterclockwise coiling of the intestines is initiated by a leftward tilt of the primitive gut tube, imparted by left-right asymmetries in the architecture of the dorsal mesentery. In silico analysis suggests that this is achieved by synergistic changes in its epithelium and mesenchyme. Within the mesenchymal compartment, cells are more densely packed on the left than on the right. In silico results indicate that this property can result from asymmetries in both extracellular matrix (ECM) and cell:cell adhesion. We find that the dorsal mesentery ECM is indeed left-right asymmetric and moreover that the adhesion molecule N-cadherin is expressed exclusively on the left side. These asymmetries are regulated by the asymmetrically expressed transcription factors Pitx2 and Isl1. Functional studies demonstrate that N-cadherin acts upstream of the changes in the ECM and is both necessary and sufficient to explain the asymmetric packing of the mesenchymal cells.

Original languageEnglish (US)
Pages (from-to)8499-8506
Number of pages8
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number25
DOIs
StatePublished - Jun 24 2008

Keywords

  • Dorsal mesentery
  • Hyaluronic acid
  • In silico modeling
  • Left-right asymmetry
  • N-cadherin

ASJC Scopus subject areas

  • General

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