Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 105, Issue 25, Pages 8499-8506Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0803578105
Keywords
left-right asymmetry; N-cadherin; dorsal mesentery; hyaluronic acid; in silico modeling
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Funding
- NICHD NIH HHS [R01 HD047360-04, R01 HD034538, R01 HD047360] Funding Source: Medline
- NIDCR NIH HHS [R01 DE016329] Funding Source: Medline
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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.
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