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: 2.44). 05/2008; 125(5-6):462-74. DOI: 10.1016/j.mod.2008.01.008
Source: PubMed


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.

Download full-text


Available from: Kazuo Ito, Jun 09, 2015

Click to see the full-text of:

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

5.51 MB

See full-text
  • Source
    • "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 "
    [Show abstract] [Hide abstract]
    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 · 2.44 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    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 · 15.05 Impact Factor
  • Source
    • "Reduced expression levels of Jagged1, Notch1, Notch4 and Delta1 in atypical chondrocytes implies that chondrocyte differentiation is associated with downregulation of these molecules. It has been shown that Jagged1mediated Notch signaling in human bone marrow stem cells is necessary to initiate chondrogenesis but must be switched off for chondrogenesis to proceed [15]. Similarly, in this study, we observed that Jagged1 was detected in the neoplastic chondroid matrix confirming that this molecule is also important as a mediator in Notch signaling during oncogenic chondrogenesis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: notch receptors are critical determinants of cell fate in a variety of organisms. Notch signaling is involved in the chondrogenic specification of neural crest cells. Aberrant Notch activity has been implicated in numerous human diseases including cancers; however its role in chondrogenic tumors has not been clarified. tissue samples from a case of primary chondrosarcoma of the maxilla and its recurrent tumor were examined immunohistochemically for Notch1-4 and their ligands (Jagged1, Jagged2 and Delta1) expression. both primary and recurrent tumors were histopathologically diagnosed as conventional hyaline chondrosarcoma (WHO Grade I). Hypercellular tumor areas strongly expressed Notch3 and Jagged1 in spindle and pleomorphic cells suggesting up-regulation of these protein molecules at sites of tumor proliferation. Expression patterns were distinct with some overlap. Differentiated malignant and atypical chondrocytes demonstrated variable expression levels of Jagged1, and weak to absent staining for Notch1, 4 and Delta1. Protein immunolocalization was largely membranous and cytoplasmic, sometimes outlining the lacunae of malignant chondrocytes. Hyaline cartilage demonstrated a diffuse or granular precipitation of Jagged1 suggesting presence of soluble Jagged1 activity at sites of abnormal chondrogenesis. No immunoreactivity for the other Notch members was observed. Calcified cartilage was consistently Notch-negative indicating down-regulation of Notch with cartilage maturation. Stromal components namely endothelial cells and fibroblasts variably expressed Notch1, 3 and Jagged1 but were mildly or non-reactive for the other members. Results indicate that Notch signaling pathway may participate in cellular differentiation and proliferation in chondrosarcoma. Findings implicate Notch3 and Jagged1 as key molecules that influence the differentiation and maturation of cells of chondrogenic lineage.
    European journal of medical research 10/2010; 15(10):456-60. DOI:10.1186/2047-783X-15-10-456 · 1.50 Impact Factor
Show more