Nakagawa, S. & Takeichi, M. Neural crest emigration from the neural tube depends on regulated cadherin expression. Development 125, 2963-2971

Department of Biophysics, Faculty of Science, Kyoto University, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
Development (Impact Factor: 6.46). 09/1998; 125(15):2963-71.
Source: PubMed


During the emergence of neural crest cells from the neural tube, the expression of cadherins dynamically changes. In the chicken embryo, the early neural tube expresses two cadherins, N-cadherin and cadherin-6B (cad6B), in the dorsal-most region where neural crest cells are generated. The expression of these two cadherins is, however, downregulated in the neural crest cells migrating from the neural tube; they instead begin expressing cadherin-7 (cad7). As an attempt to investigate the role of these changes in cadherin expression, we overexpressed various cadherin constructs, including N-cadherin, cad7, and a dominant negative N-cadherin (cN390 ), in neural crest-generating cells. This was achieved by injecting adenoviral expression vectors encoding these molecules into the lumen of the closing neural tube of chicken embryos at stage 14. In neural tubes injected with the viruses, efficient infection was observed at the neural crest-forming area, resulting in the ectopic cadherin expression also in migrating neural crest cells. Notably, the distribution of neural crest cells with the ectopic cadherins changed depending on which constructs were expressed. Many crest cells failed to escape from the neural tube when N-cadherin or cad7 was overexpressed. Moreover, none of the cells with these ectopic cadherins migrated along the dorsolateral (melanocyte) pathway. When these samples were stained for Mitf, an early melanocyte marker, positive cells were found accumulated within the neural tube, suggesting that the failure of their migration was not due to differentiation defects. In contrast to these phenomena, cells expressing non-functional cadherins exhibited a normal migration pattern. Thus, the overexpression of a neuroepithelial cadherin (N-cadherin) and a crest cadherin (cad7) resulted in the same blocking effect on neural crest segregation from neuroepithelial cells, especially for melanocyte precursors. These findings suggest that the regulation of cadherin expression or its activity at the neural crest-forming area plays a critical role in neural crest emigration from the neural tube.

Download full-text


Available from: Shinichi Nakagawa,
  • Source
    • "The case of cadherin 6 is interesting. It is normally expressed only transiently during neural crest EMT (Nakagawa and Takeichi, 1998). Cadherin 6 is important to control the apico-basal polarity via actin and active Rho distribution in fish (Clay and Halloran, 2014). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The migration of multiple cells as a cooperative unit known as collective cell migration is a common phenomenon in development, cancer and healing. Cooperation can be implemented by physical and/or chemical means and thus happens in epithelial as well as mesenchymal cell populations. Neural crest cells, a highly motile embryonic population, are a well-known model for epithelial–mesenchymal transition and cell migration. Neural crest cells use various strategies to cooperate and migrate collectively which make them a good model for the study of collectiveness. Further, neural crest cells’ interaction with other embryonic populations also relies on cell cooperation, thus providing a model for the study of cell cooperation during organogenesis.
  • Source
    • "Cadherins are adhesion molecules which form cellecell adherence junctions and also play important roles in signal transduction [18]. Cadherin-6B is expressed in the dorsal neural tube [12] [19] and is required for the epithelial mesenchymal transition (EMT) in the trunk neural crest [20] [21]. Importantly, Cadherin-6B can intrinsically activate BMP signaling independently of BMP ligands through the regulation of BMP receptors [17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cadherin-6B induces bone morphogenetic protein (BMP) signaling to promote the epithelial mesenchymal transition (EMT) in the neural crest. We have previously found that knockdown of Cadherin-6B inhibits both BMP signaling and the emigration of the early pre-migratory neural crest cells from the dorsal neural tube. In this study, we found that inhibition of BMP signaling in the neural tube, mediated by the ectopic expression of Smad-6 or Noggin, decreased the size of the Islet-1-positive dorsal cell population. Knockdown or loss of function of Cadherin-6B suppressed the generation of Islet-1-expressing cells in the dorsal neural tube, but not the Lim-1/2 positive dorsal cell population. Our results thus indicate that Cadherin-6B is necessary for the generation of Islet-1-positive dorsal interneurons, as well as the initiation of pre-migratory neural crest cell emigration. Copyright © 2015. Published by Elsevier Inc.
    Biochemical and Biophysical Research Communications 03/2015; 459(3). DOI:10.1016/j.bbrc.2015.02.136 · 2.30 Impact Factor
  • Source
    • "This process is considered hallmark of the epithelial to mesenchymal transition . N - cadherin expression has been related with increased tumor cell migration , invasion and metastasis , and with tumor angiogenesis and maintenance of tumor vasculature ( Nakagawa and Takeichi , 1998 ; Suyama et al . , 2002 ; Marambaud et al . "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian fertilization involves a series of well-orchestrated cell-cell interaction steps between gametes, as well as among spermatozoa and somatic cells of both the male and female reproductive tracts. Cadherins are Ca2+-dependent glycoproteins that have been involved in cellular adhesion and signaling in somatic cells. Taking into account that Ca2+ ions are required during fertilization, the involvement of these proteins in adhesion events during this process can be anticipated. This report presents an overview on two members of classical cadherins, Epithelial (E-) and Neural (N-) cadherin in reproductive biology. Its provides evidence of studies done by several research groups about the expression of E- and N-cadherin during spermatogenesis, oogenesis and folliculogenesis, and their involvement in gamete transport in the reproductive tracts. Moreover, it describes current knowledge of E- and N-cadherin presence in cells of the cumulus-oocyte complex and spermatozoa from several mammalian species, and shows gathered evidence on their participation in different steps of the fertilization process. A brief summary on general information of both proteins is also presented.
    Developmental Biology 01/2015; 401(1). DOI:10.1016/j.ydbio.2014.12.029 · 3.55 Impact Factor
Show more