Abstract
During Xenopus development, p120 transcripts are enriched in highly morphogenetic tissues. We addressed the developmental function of p120 by knockdown experiments and by expressing E-cadherin mutants unable to bind p120. This resulted in defective eye formation and provoked malformations in the craniofacial cartilage structures, derivatives of the cranial neural crest cells. Closer inspection showed that p120 depletion impaired evagination of the optic vesicles and migration of cranial neural crest cells from the neural tube into the branchial arches. These morphogenetic processes were also affected by p120-uncoupled cadherins or E-cadherin containing a deletion of the juxtamembrane domain. Irrespective of the manipulation that caused the malformations, coexpression of dominant-negative forms of either Rac1 or LIM kinase rescued the phenotypes. Wild-type RhoA and constitutively active Rho kinase caused partial rescue. Our results indicate that, in contrast to invertebrates, p120 is an essential factor for vertebrate development and an adequate balance between cadherin activity and cytoskeletal condition is critical for correct morphogenetic movements.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cadherins / genetics
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Cadherins / metabolism
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Catenins
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Cell Adhesion Molecules / genetics
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Cell Adhesion Molecules / metabolism*
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Cell Movement / genetics
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Craniofacial Abnormalities / genetics
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Craniofacial Abnormalities / metabolism
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Delta Catenin
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Down-Regulation / genetics
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Eye / cytology
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Eye / embryology*
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Eye / metabolism
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Eye Abnormalities / genetics
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Eye Abnormalities / metabolism
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Facial Bones / cytology
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Facial Bones / embryology*
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Facial Bones / metabolism
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Gene Deletion
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Intracellular Signaling Peptides and Proteins
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Lim Kinases
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Neural Crest / abnormalities
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Phenotype
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Protein Kinases / genetics
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Protein Kinases / metabolism
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Skull / cytology
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Skull / embryology*
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Skull / metabolism
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Xenopus laevis / embryology*
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Xenopus laevis / metabolism
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rac1 GTP-Binding Protein / genetics
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rac1 GTP-Binding Protein / metabolism
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rho-Associated Kinases
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rhoA GTP-Binding Protein / genetics
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rhoA GTP-Binding Protein / metabolism
Substances
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Cadherins
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Catenins
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Cell Adhesion Molecules
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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Protein Kinases
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Lim Kinases
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Protein Serine-Threonine Kinases
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rho-Associated Kinases
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rac1 GTP-Binding Protein
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rhoA GTP-Binding Protein
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Delta Catenin