For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
37
references
 Top references
cited by
20
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      293
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      An Epigenetic Feedback Regulatory Loop Involving MicroRNA-195 and MBD1 Governs Neural Stem Cell Differentiation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play pivotal roles in stem cell biology. Methyl-CpG binding protein 1 (MBD1), an important epigenetic regulator of adult neurogenesis, controls the proliferation and differentiation of adult neural stem/progenitor cells (aNSCs). We recently demonstrated that MBD1 deficiency in aNSCs leads to altered expression of several noncoding microRNAs (miRNAs).

          Methodology/Principal Findings

          Here we show that one of these miRNAs, miR-195, and MBD1 form a negative feedback loop. While MBD1 directly represses the expression of miR-195 in aNSCs, high levels of miR-195 in turn repress the expression of MBD1. Both gain-of-function and loss-of-function investigations show that alterations of the MBD1–miR-195 feedback loop tip the balance between aNSC proliferation and differentiation.

          Conclusions/Significance

          Therefore the regulatory loop formed by MBD1 and miR-195 is an important component of the epigenetic network that controls aNSC fate.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.

          Ruthie Amir, Ignatia B Van den Veyver, Mimi Wan … (1999)
          Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder and one of the most common causes of mental retardation in females, with an incidence of 1 in 10,000-15,000 (ref. 2). Patients with classic RTT appear to develop normally until 6-18 months of age, then gradually lose speech and purposeful hand use, and develop microcephaly, seizures, autism, ataxia, intermittent hyperventilation and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. As RTT occurs almost exclusively in females, it has been proposed that RTT is caused by an X-linked dominant mutation with lethality in hemizygous males. Previous exclusion mapping studies using RTT families mapped the locus to Xq28 (refs 6,9,10,11). Using a systematic gene screening approach, we have identified mutations in the gene (MECP2 ) encoding X-linked methyl-CpG-binding protein 2 (MeCP2) as the cause of some cases of RTT. MeCP2 selectively binds CpG dinucleotides in the mammalian genome and mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A (refs 12,13). In 5 of 21 sporadic patients, we found 3 de novo missense mutations in the region encoding the highly conserved methyl-binding domain (MBD) as well as a de novo frameshift and a de novo nonsense mutation, both of which disrupt the transcription repression domain (TRD). In two affected half-sisters of a RTT family, we found segregation of an additional missense mutation not detected in their obligate carrier mother. This suggests that the mother is a germline mosaic for this mutation. Our study reports the first disease-causing mutations in RTT and points to abnormal epigenetic regulation as the mechanism underlying the pathogenesis of RTT.
          Article 0 comments Cited 1155 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A MicroRNA feedback circuit in midbrain dopamine neurons.

            Jongpil Kim, Keiichi Inoue, Jennifer Ishii … (2007)
            MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide, non-protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons (DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs and is deficient in midbrain tissue from patients with Parkinson's disease. miR-133b regulates the maturation and function of midbrain DNs within a negative feedback circuit that includes the paired-like homeodomain transcription factor Pitx3. We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion.
            Article 0 comments Cited 377 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus.

              Chunmei Zhao, E. Teng, Robert Summers … (2006)
              Adult neurogenesis in the dentate gyrus may contribute to hippocampus-dependent functions, yet little is known about when and how newborn neurons are functional because of limited information about the time course of their connectivity. By using retrovirus-mediated gene transduction, we followed the dendritic and axonal growth of adult-born neurons in the mouse dentate gyrus and identified distinct morphological stages that may indicate different levels of connectivity. Axonal projections of newborn neurons reach the CA3 area 10-11 d after viral infection, 5-6 d before the first spines are formed. Quantitative analyses show that the peak of spine growth occurs during the first 3-4 weeks, but further structural modifications of newborn neurons take place for months. Moreover, the morphological maturation is differentially affected by age and experience, as shown by comparisons between adult and postnatal brains and between housing conditions. Our study reveals the key morphological transitions of newborn granule neurons during their course of maturation.
              Article 0 comments Cited 344 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Andre Van Wijnen: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2013
                Publication date (Electronic): 17 January 2013
                Volume: 8
                Issue: 1
                Electronic Location Identifier: e51436
                Affiliations
                [1 ]Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                [2 ]Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, New Mexico, United States of America
                [3 ]Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                [4 ]Department of Neuroscience, University of Wisconsin-Madison, Madison, Wisconsin, United States of America
                University of Massachusetts, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: XZ CL. Performed the experiments: ZT ALM EJ CCC SvH MDR EP YX YL WG. Analyzed the data: ALM CL XZ. Wrote the paper: CL ALM XZ.

                [¤]

                Current address: Graduate Program in Neurobiology and Behavior, University of Washington, Seattle, Washington, United States of America

                Article
                Publisher ID: PONE-D-12-25131
                DOI: 10.1371/journal.pone.0051436
                PMC ID: 3547917
                PubMed ID: 23349673
                SO-VID: 4aeb5f6a-8e46-4f36-a6b9-ba5d0c8146a1
                Copyright statement: Copyright @ 2013
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 20 August 2012
                Date accepted : 31 October 2012
                Page count
                Pages: 12
                Funding
                This work was supported by grants from the National Institutes of Health (NIH) (MH080434, MH07897) and the International Rett Syndrome Foundation (IRSF) to X.Z.; a center grant from the NIH to the Waisman Center (P30HD03352); Postbaccalaureate Research and Education Program fellowships (PREP; NIH/R25 GM075149) to C.C.C. and A.L.M.; an NIH Molecular Biosciences Training grant (MBTG: T32 GM07215) to E.M.J.; a Minority Access to Research Careers fellowship (MARC, NIH/T34 GM008510) to M.D.R; and a postdoctoral fellowship from University of Wisconsin-Madison Center for Stem Cells and Regenerative Medicine to W.G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology
                Subject: Developmental Biology
                Subject: Stem Cells
                Subject: Neural Stem Cells
                Subject: Cell Differentiation
                Subject: Cell Fate Determination
                Subject: Genetics
                Subject: Epigenetics
                Subject: Molecular Cell Biology
                Subject: Cellular Types
                Subject: Stem Cells
                Subject: Neural Stem Cells
                Subject: Neuroscience
                Subject: Developmental Neuroscience
                Subject: Neural Stem Cells

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content293

                See all similar

                Cited by19

                See all cited by

                Most referenced authors973

                See all reference authors