PUBLICATION

Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology

Authors
Jülich, D., Cobb, G., Melo, A.M., McMillen, P., Lawton, A.K., Mochrie, S.G., Rhoades, E., Holley, S.A.
ID
ZDB-PUB-150623-8
Date
2015
Source
Developmental Cell   34(1): 33-44 (Journal)
Registered Authors
Holley, Scott, Jülich, Dörthe, Lawton, Angela
Keywords
none
MeSH Terms
  • Animals
  • Cadherins/metabolism
  • Cell Adhesion/physiology
  • Cell Membrane/metabolism
  • Extracellular Matrix/metabolism*
  • Extracellular Matrix Proteins/metabolism*
  • Fibronectins/metabolism*
  • Integrins/metabolism*
  • Somites/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism
PubMed
26096733 Full text @ Dev. Cell
Abstract
The diverse morphologies of animal tissues are underlain by different configurations of adherent cells and extracellular matrix (ECM). Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin α5. Fluorescence cross-correlation spectroscopy within the zebrafish paraxial mesoderm mesenchyme reveals a physical association between Integrin α5 on adjacent cell membranes. This Integrin-Integrin complex correlates with conformationally inactive Integrin. Cadherin 2 stabilizes both the Integrin association and inactive Integrin conformation. Thus, Integrin repression within the adherent mesenchymal interior of the tissue biases Fibronectin fibrillogenesis to the tissue surface lacking cell-cell adhesions. Along nascent somite boundaries, Cadherin 2 levels decrease, becoming anti-correlated with levels of Integrin α5. Simultaneously, Integrin α5 clusters and adopts the active conformation and then commences ECM assembly. This cross-scale regulation of Integrin activation organizes a stereotypic pattern of ECM necessary for vertebrate body elongation and segmentation.
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