miRNA-MEDIATED MODULATION OF NEURAL PROGENITOR CELL FATE

Summary

Principal Investigator: Beverly Davidson
Abstract: DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) are noncoding RNAs expressed within the genomes of multiple species. Prior work has demonstrated that miRNAs are expressed in developing and adult tissues, and their expression can be constitutive, temporal, ubiquitous, or cell-specific. A new class of negative regulators of expression, miRNAs work by inhibiting translation of target messenger RNAs (mRNAs) via base pairing with mRNA 3'untranslated regions. This process is called RNA interference (RNAi). Since the discovery of RNAi in worms, which was awarded the Nobel prize in physiology or medicine in 2006, studies of naturally occurring RNAi in developing vertebrate organs and in adult animals have revealed their important contribution to cellular phenotypes. Recent work has shown that miRNAs participate in teratogen-mediated changes. We also know that teratogens impair proliferation of neural progenitors. What we do not know, however, is the interface between miRNAs and neural progenitor cell maintenance, proliferation and differentiation. In this proposal we will first use a focused approach to assess how a candidate miRNA, miR-34a, participates in cell fate decisions in neural progenitor cells in culture and in vivo. In additional studies we will ascertain how perturbing miR-34a levels impacts target protein expression. Two aims are proposed. In Aim 1 we will use anti-miRs and miRexpression vectors to test how miR-34a impacts neuronal differentiation in loss- and gain- of function experiments, respectively, in vitro and in vivo. In Aim 2 we will use anti-miRs and miR-expression vectors to test how miR-34a levels effects miR-34a target proteins.
Funding Period: 2008-06-01 - 2010-05-31
more information: NIH RePORT

Top Publications

  1. pmc The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease
    Amy N Packer
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurosci 28:14341-6. 2008
  2. pmc MiR-34a represses Numbl in murine neural progenitor cells and antagonizes neuronal differentiation
    Sarah K Fineberg
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America
    PLoS ONE 7:e38562. 2012
  3. pmc Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis
    H S McLoughlin
    Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52240, USA
    Neuroscience 223:285-95. 2012
  4. pmc Transcriptome-wide discovery of microRNA binding sites in human brain
    Ryan L Boudreau
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Neuron 81:294-305. 2014
  5. ncbi MicroRNAs potentiate neural development
    Sarah K Fineberg
    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242 USA
    Neuron 64:303-9. 2009
  6. pmc Structure and activity of putative intronic miRNA promoters
    Alex Mas Monteys
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    RNA 16:495-505. 2010

Detail Information

Publications6

  1. pmc The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease
    Amy N Packer
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Neurosci 28:14341-6. 2008
    ..These data provide evidence for a double negative feedback loop between the REST silencing complex and the miRNAs it regulates...
  2. pmc MiR-34a represses Numbl in murine neural progenitor cells and antagonizes neuronal differentiation
    Sarah K Fineberg
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa, United States of America
    PLoS ONE 7:e38562. 2012
    ..This work extends our understanding of miR-34a-mediated control of cell differentiation from cancer to mammalian nervous system development...
  3. pmc Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis
    H S McLoughlin
    Interdisciplinary Graduate Program in Neuroscience, University of Iowa, Iowa City, IA 52240, USA
    Neuroscience 223:285-95. 2012
    ..These results significantly extend earlier works, and emphasize the impact of miRNAs on neural progenitor cell proliferation, apoptosis, migration, and differentiation in the developing mammalian brain...
  4. pmc Transcriptome-wide discovery of microRNA binding sites in human brain
    Ryan L Boudreau
    Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA
    Neuron 81:294-305. 2014
    ..We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics...
  5. ncbi MicroRNAs potentiate neural development
    Sarah K Fineberg
    Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242 USA
    Neuron 64:303-9. 2009
    ....
  6. pmc Structure and activity of putative intronic miRNA promoters
    Alex Mas Monteys
    Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    RNA 16:495-505. 2010
    ..These data support complex regulation of intronic miRNA expression, and have relevance to disregulation in disease settings...