Essential roles of fibronectin in the development of the left–right embryonic body plan

Studies in Xenopus laevis suggested that cell-extracellular matrix (ECM) interactions regulate the development of the left–right axis of asymmetry; however, the identities of ECM components and their receptors important for this process have remained unknown. We discovered that FN is required for th...

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Bibliographic Details
Published in:Developmental biology 2011-06, Vol.354 (2), p.208-220
Main Authors: Pulina, Maria V., Hou, Shuan-Yu, Mittal, Ashok, Julich, Dorthe, Whittaker, Charlie A., Holley, Scott A., Hynes, Richard O., Astrof, Sophie
Format: Article
Language:English
Subjects:
Animals
Body Patterning
Extracellular Matrix - metabolism
Extracellular Matrix Proteins - metabolism
Fibronectin
fibronectins
Fibronectins - genetics
Fibronectins - physiology
fish
Fishes - embryology
Fishes - growth & development
gene expression regulation
Gene Expression Regulation, Developmental
Hedgehog Proteins - metabolism
Integrin alpha 5
Integrin alpha5beta1 - metabolism
integrins
Left-Right Determination Factors - metabolism
Lefty
Left–right asymmetry
Mice
morphogenesis
mutants
Nodal
Notochord - embryology
Notochord - growth & development
Pitx2c
receptors
Signal Transduction
SMAD
Smad2 Protein - metabolism
Smad3 Protein - metabolism
Wnt Proteins - metabolism
Xenopus laevis
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Summary:Studies in Xenopus laevis suggested that cell-extracellular matrix (ECM) interactions regulate the development of the left–right axis of asymmetry; however, the identities of ECM components and their receptors important for this process have remained unknown. We discovered that FN is required for the establishment of the asymmetric gene expression pattern in early mouse embryos by regulating morphogenesis of the node, while cellular fates of the nodal cells, canonical Wnt and Shh signaling within the node were not perturbed by the absence of FN. FN is also required for the expression of Lefty 1/2 and activation of SMADs 2 and 3 at the floor plate, while cell fate specification of the notochord and the floor plate, as well as signaling within and between these two embryonic organizing centers remained intact in FN-null mutants. Furthermore, our experiments indicate that a major cell surface receptor for FN, integrin α5β1, is also required for the development of the left–right asymmetry, and that this requirement is evolutionarily conserved in fish and mice. Taken together, our studies demonstrate the requisite role for a structural ECM protein and its integrin receptor in the development of the left–right axis of asymmetry in vertebrates. ► Formation of left–right axis of asymmetry was investigated in fibronectin-null mice. ► We found that fibronectin (FN) is required for the morphogenesis of the node. ► FN is not required for cell fate specification in the node or midline. ► FN is required for the expression of Lefty1 and SMAD activation in the floor plate. ► Integrin α5 is required for left–right morphogenesis of the heart in mice and fish.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2011.03.026