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Dev Cell. 2015 Jul 6;34(1):33-44. doi: 10.1016/j.devcel.2015.05.005. Epub 2015 Jun 18.

Cross-Scale Integrin Regulation Organizes ECM and Tissue Topology.

Author information

1
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
3
Department of Physics, Yale University, New Haven, CT 06511, USA.
4
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA. Electronic address: scott.holley@yale.edu.

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.

PMID:
26096733
PMCID:
PMC4496283
DOI:
10.1016/j.devcel.2015.05.005
[Indexed for MEDLINE]
Free PMC Article

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