Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of cell differentiation is an important assignment for cellular engineering. One of the techniques for regulation is gene transfection into undifferentiated cells. Transient expression of NeuroD2, one of neural bHLH transcription factors, converted mouse N1E-115 neuroblastoma cells into differentiated neurons. The regulation of neural bHLH expression should be a novel strategy for cell differentiation. In this study, we tried to regulate neural differentiation by NeuroD2 gene inserted under the control of heat shock protein-70 (HSP) promoter, which can be activated by electrical stimulation. Mouse neuroblastoma cell line, N1E-115, was stably transfected with expression vector containing mouse NeuroD2 cDNA under HSP promoter. Transfected cells were cultured on the electrode surface and applied electrical stimulation. After stimulation, NeuroD2 expression was induced, and transfected cells adopt a neuronal morphology at 3 days after stimulation. These results suggest that neural differentiation can be induced by electrically stimulated gene expression of NeuroD2.
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PMID:Induction of neural differentiation by electrically stimulated gene expression of NeuroD2. 1244 54

NeuroD2, one of the neurospecific basic helix-loop-helix transcription factors, has the ability to induce neural differentiation in undifferentiated cells. In this paper, we show that transduction of NeuroD2 protein induced mouse neuroblastoma cell line N1E-115 into neural differentiation. NeuroD2 has two basic-rich domains, one is nuclear localization signal (NLS) and the other is basic region of basic helix-loop-helix (basic). We constructed some mutants of NeuroD2, ND2(Delta100-115) (lack of NLS), ND2(Delta123-134) (lack of basic) and ND2(Delta100-134) (lack of both NLS and basic) for transduction experiments. Using these proteins, we have shown that NLS region of NeuroD2 plays a role of protein transduction. Continuous addition of NeuroD2 protein resulted in N1E-115 cells adopting neural morphology after 4 days and Tau mRNA expression was increased. These results suggest that neural differentiation can be induced by direct addition of NeuroD2 protein.
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PMID:Transduction of NeuroD2 protein induced neural cell differentiation. 1673 Aug 30

Pro-neural basic helix loop helix (bHLH) transcription factors are involved in many aspects of normal neuronal development, and over-expression of genes for several of these factors has been shown to induce aspects of neuronal differentiation in cell lines and stem cells. Here we show that over-expression of NeuroD2 (ND2), Neurogenin1 and 2 leads to morphological differentiation of N18-RE-105 neuroblastoma cells and increased expression of synaptic proteins. Particularly ND2 induced neurite formation and increases in the expression of synaptic proteins such as synaptotagmin, that is not expressed normally in this cell type, as well as the redistribution of another synaptic protein, SNAP25, to a cell membrane location. Infection of human neural progenitor cells using adeno associated viral (AAV) vectors also promoted neuronal differentiation. Over-expressing cells demonstrated a significant increase in the neuron specific form of tubulin as well as increased expression of synaptotagmin. Genetic modification of neural progenitor cell with bHLH factors such as ND2 may be a viable strategy to enhance differentiation of these cells into replacement neurons for human disease.
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PMID:Induction of neural differentiation by the transcription factor neuroD2. 2219 73

Cell fate determination and differentiation during neurogenesis and myogenesis involve the sequential expression of several basic helix-loop-helix (bHLH) transcription factors. The expression of NeuroD1/2 and the expression of NSCL(Nhlh)1/2 are closely related in many developing peripheral and central neuronal cells, suggesting an epistatic relationship between these two bHLH transcription factor families during neurogenesis. To investigate this relationship, a murine neuroblastoma cell culture system and single/double knock-out (KO) mice of NeuroD1 and NeuroD2 were utilized for the gain-of-function and loss-of-function approaches, respectively. Both NeuroD1 and NeuroD2 were able to induce the transcription of NSCL1 in vitro; however, they were not able to activate NSCL2 transcription. The DNA-binding ability of NeuroD1 was essential for NSCL1 induction. To examine the epistatic relationship in vivo, we examined the expression of NSCL1 and NSCL2 in NeuroD1 and NeuroD2 KO mice and NeuroD1/2 compound KO mice by in situ hybridization, RT-PCR and Northern blotting. The expression of NSCL1 was lower in the NeuroD1 KO mice and was not further decreased in the double KO mice. However, the expression of NSCL2 did not change in either the single KO or double KO mice. These results demonstrate that NeuroD1 is an upstream regulator of the NSCL1 gene but not the NSCL2 gene in mice. In addition, NeuroD2 is not involved in this regulatory pathway in vivo.
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PMID:NeuroD1 is an upstream regulator of NSCL1. 2231 Jul 18