Congenital Hypomyelinating Neuropathy with Lethal Conduction Failure in Mice Carrying the Egr2 I268N Mutation

Baloh, Robert H.; Strickland, Amy; Ryu, Elizabeth J.; Le, Nam; Fahrner, Timothy J.; Yang, Minji; Nagarajan, Rakesh; Milbrandt, Jeffrey

doi:10.1523/jneurosci.2168-08.2009

Cited by 41 publications

(32 citation statements)

References 56 publications

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“…A battery of locomotion and behavioural tests (Supplementary Fig. 2d; Supplementary Movie 3) indicated peripheral nerve disease as reported in other mouse models of peripheral neuropathy 22–24 .…”

Section: Resultssupporting

confidence: 64%

The tumour suppressor LKB1 regulates myelination through mitochondrial metabolism

et al. 2014

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A prerequisite to myelination of peripheral axons by Schwann cells (SCs) is SC differentiation, and recent evidence indicates that reprogramming from a glycolytic to oxidative metabolism occurs during cellular differentiation. Whether this reprogramming is essential for SC differentiation, and the genes that regulate this critical metabolic transition are unknown. Here we show that the tumour suppressor Lkb1 is essential for this metabolic transition and myelination of peripheral axons. Hypomyelination in the Lkb1-mutant nerves and muscle atrophy lead to hindlimb dysfunction and peripheral neuropathy. Lkb1-null SCs failed to optimally activate mitochondrial oxidative metabolism during differentiation. This deficit was caused by Lkb1-regulated diminished production of the mitochondrial Krebs cycle substrate citrate, a precursor to cellular lipids. Consequently, myelin lipids were reduced in Lkb1-mutant mice. Restoring citrate partially rescued Lkb1-mutant SC defects. Thus, Lkb1-mediated metabolic shift during SC differentiation increases mitochondrial metabolism and lipogenesis, necessary for normal myelination.

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Section: Resultssupporting

confidence: 64%

The tumour suppressor LKB1 regulates myelination through mitochondrial metabolism

et al. 2014

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“…For example, in Schwann cells, EGR2 promotes the expression of P27, the homolog of C. elegans CKI-1, and acts with NAB proteins to promote terminal differentiation (Fig. 7B) (Parkinson et al, 2004;Baloh et al, 2009). Mammalian homologs of other C. elegans heterochronic genes also control differentiation.…”

Section: Homologs Of Mab-10 Lin-29 Lin-28 and Nhr-25 Regulate Cellumentioning

confidence: 99%

MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the transition from larva to adult in C. elegans

Harris

Horvitz

2011

Development

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SUMMARYIn Caenorhabditis elegans, a well-defined pathway of heterochronic genes ensures the proper timing of stage-specific developmental events. During the final larval stage, an upregulation of the let-7 microRNA indirectly activates the terminal differentiation factor and central regulator of the larval-to-adult transition, LIN-29, via the downregulation of the let-7 target genes lin-41 and hbl-1. Here, we identify a new heterochronic gene, mab-10, and show that mab-10 encodes a NAB (NGFI-Abinding protein) transcriptional co-factor. MAB-10 acts with LIN-29 to control the expression of genes required to regulate a subset of differentiation events during the larval-to-adult transition, and we show that the NAB-interaction domain of LIN-29 is conserved in Kruppel-family EGR (early growth response) proteins. In mammals, EGR proteins control the differentiation of multiple cell lineages, and EGR-1 acts with NAB proteins to initiate menarche by regulating the transcription of the luteinizing hormone  subunit. Genome-wide association studies of humans and various studies of mouse recently have implicated the mammalian homologs of the C. elegans heterochronic gene lin-28 in regulating cellular differentiation and the timing of menarche. Our work suggests that human homologs of multiple C. elegans heterochronic genes might act in an evolutionarily conserved pathway to promote cellular differentiation and the onset of puberty.

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“…In humans, defect of the egr2 gene causes type 1 Charcot-Marie-Tooth syndrome and congenital hypomyelinating neuropathy [25,26]. EGR2 is also associated with the development of myelination in the peripheral nervous system.…”

Section: Introductionmentioning

confidence: 99%

miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer

Liu¹,

Shi²,

Liu³

et al. 2015

ABBS

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Non-small-cell lung cancer (NSCLC) is one of the most common lung cancers, and microRNAs (miRNAs) have been reported to play essential roles in NSCLC. Recent studies have indicated that miR-330-3p expression is up-regulated in NSCLC samples and in tissues of NSCLC brain metastasis. In this study, up-regulation of miR-330-3p expression was confirmed in NSCLC and 20 NSCLC patient samples. Furthermore, miR-330-3p was over-expressed in NSCLC cell lines A549 and H23, and the promotive function of miR-330-3p was investigated in regulating NSCLC cell proliferation and cell cycle distribution. To identify potential target genes of miR-330-3p in NSCLC, the miRNA target prediction databases were used. Luciferase activity assay and real-time RT-PCR analysis confirmed that miR-330-3p is negatively correlated with the expression of early growth response 2 (EGR2). Moreover, it was also found that EGR2 mRNA contains two potential binding sites for miR-330-3p. Knock-down of EGR2 with siRNA was demonstrated to have a similar effect as the over-expression of miR-330-3p in NSCLC cell lines. Taken together, our results show that EGR2 is a target of miR-330-3p.

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Congenital Hypomyelinating Neuropathy with Lethal Conduction Failure in Mice Carrying the Egr2 I268N Mutation

Cited by 41 publications

References 56 publications

The tumour suppressor LKB1 regulates myelination through mitochondrial metabolism

The tumour suppressor LKB1 regulates myelination through mitochondrial metabolism

MAB-10/NAB acts with LIN-29/EGR to regulate terminal differentiation and the transition from larva to adult in C. elegans

miR-330-3p controls cell proliferation by targeting early growth response 2 in non-small-cell lung cancer

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