Cellular localization and signaling activity of beta-catenin in migrating neural crest cells.
In the vertebrate embryo, development of the neural crest is accompanied by sequential changes in cellular adhesiveness, allowing cells to delaminate from the neural epithelium, to undergo migration through extracellular matrix material, and to coalesce into ganglia of the peripheral nervous system. Because of its dual role in cell adhesion, as a link between cadherins and the actin cytoskeleton, and in cell signaling, as a key mediator of the Wnt-signaling pathway, beta-catenin is a good candidate to play a central role in the control of neural crest cell development. In the present study, we analyzed, by using an in vitro culture system, whether the cellular localization and the signaling activity of beta-catenin are regulated in conjunction with cell migration during ontogeny of trunk neural crest cells in the avian embryo. beta-Catenin molecules were found primarily in association with N-cadherin in the regions of intercellular contacts in most migrating neural crest cells, and only early-migrating cells situated in proximity with the dorsal side of the neural tube showed detectable beta-catenin in their nuclei. This finding indicates that beta-catenin may be recruited for signaling in neural crest cells only transiently at the onset of migration and that sustained beta-catenin signals are not necessary for the progression of migration. The nuclear distribution of beta-catenin within crest cells was not affected upon modification of the N-cadherin-mediated cell-cell contacts, revealing that recruitment of beta-catenin for signaling is not driven by changes in intercellular cohesion during migration. Overstimulation of beta-catenin signals in neural crest cells at the time of their migration, using LiCl treatment or coculture with Wnt-1-producing cells, induced nuclear translocation of beta-catenin and Lef-1 up-regulation in neural crest cells and provoked a marked inhibition of cell delamination and migration. The effect of LiCl and exogenous Wnt-1 on neural crest cells could be essentially attributed to a dramatic decrease in integrin-mediated cell-matrix adhesion as well as a massive reduction of cell proliferation. In addition, although it apparently did not affect expression of neural crest markers, Wnt-1 exposure dramatically affected signaling events involving Notch-Delta, presumably also accounting for the strong reduction in cell delamination. In conclusion, our data indicate that beta-catenin functions primarily in cell adhesion events during migration and may be recruited transiently for signaling during delamination possibly to regulate the balance between cell proliferation and cell differentiation.
de Melker
Annemieke A
AA
Laboratoire de Biologie du Développement, CNRS et Université Pierre et Marie Curie, Paris, France.
Desban
Nathalie
N
Duband
Jean-Loup
JL
D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion; D002450:Cell Communication; D016923:Cell Death; D002454:Cell Differentiation; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009432:Neural Crest / Q000166:cytology* / Q000196:embryology*; D009474:Neurons / Q000378:metabolism; D011784:Quail; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology; D015854:Up-Regulation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin
D000199:Actins; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D014357:Trypsin; D018021:Lithium Chloride