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.

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Available from: Shinichi Nakagawa, Oct 05, 2015
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    • "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). "
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    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.
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    • "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]. "
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    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
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    • "Cadherin-7 (Cdh7) expression in the chicken SP was described before by Nakagawa and Takeichi (1998) and by our group. For example, it has been reported that Cdh7 is expressed in a radial domain (Nakagawa and Takeichi, 1998) that abuts ventrally the basal/alar plate boundary (Ju et al., 2004). In the SP, sonic hedgehog regulates its expression (Luo et al., 2006). "
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    ABSTRACT: Classic cadherins belong to the family of cadherin genes and play important roles in neurogenesis, neuron migration, and axon growth. In the present study, we compared the expression patterns of 10 classic cadherins (Cdh2, Cdh4, Cdh6, Cdh7, Cdh8, Cdh9, Cdh11, Cdh12, Cdh18, and Cdh20) in the developing chicken spinal cord (SP) by in situ hybridization. Our results indicate that each of the investigated cadherins exhibits a spatially restricted and temporally regulated pattern of expression. At early developmental stages (E2.5-E3), Cdh2 is expressed throughout the neuroepithelial layer. Cdh6 is strongly positive in the roof plate and later also in the floor plate. Cdh7, Cdh11, Cdh12, and Cdh20 are expressed in restricted regions of the basal plate of the SP. At intermediate stages of development (E4-E10), specific expression profiles are observed for all investigated cadherins in the differentiating mantle layer along the dorsoventral, mediolateral, and rostrocaudal dimensions. Expression profiles are especially diverse for Cdh2, Cdh4, Cdh8, Cdh11, and Cdh20 in the dorsal horn, while different pools of motor neurons exhibit signal for Cdh6, Cdh7, Cdh8, Cdh9, Cdh12, and Cdh20 in the ventral horn. Interestingly, subpopulations of cells in the dorsal root ganglion express combinations of different cadherins. In the surrounding tissues, such as the boundary cap cells and the notochord, the cadherins are also expressed differentially. The highly regulated spatiotemporal expression patterns of the classic cadherins indicate that these genes potentially play multiple and diverse roles during the development of the SP and its surrounding tissues.
    Frontiers in Neuroanatomy 03/2014; 8:18. DOI:10.3389/fnana.2014.00018 · 3.54 Impact Factor
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