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Different downstream pathways for Notch signaling are required for gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells

Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.
Mechanisms of development (Impact Factor: 2.24). 05/2008; 125(5-6):462-74. DOI: 10.1016/j.mod.2008.01.008
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ABSTRACT We examined the roles of Notch signaling and fibroblast growth factors (FGFs) in the gliogenesis of mouse mesencephalic neural crest cells. The present study demonstrated that Notch activation or FGF treatment promotes the differentiation of glia expressing glial fibrillary acidic protein. Notch activation or FGF2 exposure during the first 48 h in culture was critical for glial differentiation. The promotion of gliogenesis by FGF2 was significantly suppressed by the inhibition of Notch signaling using Notch-1 siRNA. These data suggest that FGFs activate Notch signaling and that this activation promotes the gliogenic specification of mouse mesencephalic neural crest cells. Notch activation and FGF treatment have been shown to participate in the chondrogenic specification of these cells [Nakanishi, K., Chan, Y.S., Ito, K., 2007. Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 124, 190-203]. Therefore, we analyzed whether or not there were differences between gliogenic and chondrogenic specifications in the downstream pathway of the Notch receptor. Whereas the activation of only the Deltex-mediated pathway was sufficient to promote glial specification, the activation of both RBP-J- and Deltex-dependent pathways was required for chondrogenic specification. These results suggest that the different downstream pathways of the Notch receptor participate in the gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells.

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    • "The siRNA was prepared as described previously (Nakanishi et al., 2007; Ijuin et al., 2008). The siRNA duplexes for p50 subunit of NF-jB, Deltex-1, and Notch-1 were designed on the basis of p50, and Deltex-1, Notch-1 sequences published online "
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    ABSTRACT: In the present study, we elucidated that nuclear factor-κB (NF-κB) participates in the gliogenic specification of mouse mesencephalic neural crest cells. Whereas transfection of the NF-κB expression vector stimulated gliogenesis, treatment with the dominant negative NF-κB expression vector or NF-κB small interfering RNA suppressed the promotion of gliogenic specification by FGF treatment or Notch activation. This suppression was recovered by the treatment with the Deltex-1 expression vector or mammalian hairy and enhancer of split homologs expression vectors. Furthermore, transfection of the inhibitor of κB (IκB) expression vector inhibited gliogenesis. In addition, treatment with the NF-κB expression vector promoted the expression of Deltex-1. These data suggest that NF-κB signaling is implicated in the gliogenesis through the interaction with Notch signaling. Moreover, cells that contain Sox10 expressed NF-κB and Deltex-1 in the presumptive trigeminal ganglia of embryonic day 9.0-9.5 mouse embryos. This observation supports our notion that the interaction between NF-κB signaling and Notch signaling plays an important role in the gliogenic specification of mouse mesencephalic neural crest cells.
    Mechanisms of development 09/2011; 128(7-10):496-509. DOI:10.1016/j.mod.2011.09.003 · 2.24 Impact Factor
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    • "While the molecular mechanisms by which Numb and Numbl regulate neural development are still being sorted out, the identification of ACBD3 as a relevant player provides an exciting new direction for consideration. The Dx proteins (of which there are four in mammals, Dtx1–4) are ring domain E3 ubquitin ligases that regulate Notch receptor trafficking (Ijuin et al., 2008; Mukherjee et al., 2005; Wilkin et al., 2008; Wilkin and Baron, 2005; Yamada et al., 2011). However, the role of Dx in development is complex, as it seems able to both positively and negatively regulate Notch (Martinez Arias et al., 2002; Matsuno et al., 1998; Patten et al., 2006; Sestan et al., 1999; Xu and Artavanis-Tsakonas, 1990). "
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    ABSTRACT: The Notch pathway is prominent among those known to regulate neural development in vertebrates. Notch receptor activation can inhibit neurogenesis, maintain neural progenitor character, and in some contexts promote gliogenesis and drive binary fate choices. Recently, a wave of exciting studies has emerged, which has both solidified previously held assertions and expanded our understanding of Notch function during neurogenesis and in the adult brain. These studies have examined pathway regulators and interactions, as well as pathway dynamics, with respect to both gene expression and cell-cell signaling. Here, focusing primarily on vertebrates, we review the current literature on Notch signaling in the nervous system, and highlight numerous recent studies that have generated interesting and unexpected advances.
    Neuron 03/2011; 69(5):840-55. DOI:10.1016/j.neuron.2011.02.031 · 15.98 Impact Factor
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    • "Primary cultures of mesencephalic neural crest cells were prepared from E8.0 (6-to 8-somite stages) ddY mouse embryos (Ito and Morita, 1995; Kubota and Ito, 2000; Ota and Ito, 2003; Nakanishi et al., 2007; Ijuin et al., 2008). Neural folds at the mesencephalic levels were dissected and cut into fragments . "
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    ABSTRACT: Fibroblast growth factors (FGFs) have been shown to promote the chondrogenic and gliogenic specification of mouse mesencephalic neural crest cells through Notch signaling [Nakanishi, K., Chan, S.Y., Ito, K., 2007. Notch signaling is required for the chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 124, 190-203; Ijuin, K., Nakanishi, K., Ito, K., 2008. Different downstream pathways for Notch signaling are required for gliogenic and chondrogenic specification of mouse mesencephalic neural crest cells. Mech. Dev. 125, 462-474]. In the present study, we analyzed FGF signaling pathways in chondrogenic and gliogenic specification. The promotion of chondrogenesis by FGF-2 was significantly suppressed by U0126, an inhibitor of the extracellular signal-regulated protein kinase (Erk) pathway, and by Erk-1 siRNA. Chondrogenesis was also prevented by the dominant negative Ets-1 expression vector. In contrast, Ets-1 was irrelevant to gliogenesis. The promotion of gliogenesis by FGF-2 was not only inhibited by U0126 but also by LY294002 and rapamycin, inhibitors of the Akt pathway, and by Akt-1 siRNA. Furthermore, gliogenesis was dramatically prevented by blocking the expression of p70S6 kinase (p70S6k), which is activated by both the Erk and Akt pathways, with p70S6k siRNA. These results suggest that Ets-1 activated by the Erk pathway promotes chondrogenic specification and p70S6k activated by both the Erk and Akt pathways plays an important role in gliogenic specification.
    Mechanisms of development 04/2010; 127(3-4):169-82. DOI:10.1016/j.mod.2010.01.002 · 2.24 Impact Factor
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