Claudia Barros Lab - Neural Stem Cell Research

Image shows Neural Stem Cells (green, GFP) inside the Drosophila brain, some about to divide (red, CyclinB). Courtesy of Claudia Barros Lab

Postnatal neurogenesis promotes brain plasticity and function. Intrinsic and extrinsic signals converge to promote appropriate postembryonic NSC development and maintenance. Restricting NSC potential is equally vital as the expansion of aberrant neural stem-like cells can lead to brain tumour growth.

Our main goal is to identify fundamental intrinsic Neural Stem Cell (NSC) properties and extrinsic niche signals regulating the pace of postembryonic neurogenesis in both health and in disease, such as upon neoplastic transformation. We use a well-known genetically tractable in vivo model - the fruit fly Drosophila brain - and translate findings into mammalian systems, as well as human brain samples.

Current projects in the laboratory address three major questions in NSC biology:

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Q1: How do NSCs transit from a quiescent to a mitotically active state?
As in mammals, Drosophila postembryonic NSCs transit from quiescence to a mitotically active state to generate adult brain neurons and glia. The mechanisms underlying NSC mitotic reactivation remain largely unknown. We are screening and characterising the role of genes involved in this process using Drosophila, and aim at investigating conserved functions in mammalian systems.

Q2: How is the identity of different NSCs established?
It is becoming increasingly clear that the developing and adult mammalian brain harbours distinct NSC types. Yet, information about their molecular identity is currently at its infancy. The identification of different NSC types in the Drosophila larval brain, the evolutionary conservation of regulatory mechanisms, and the genetic tools available prompted us to use Drosophila as a model to identify novel NSC type-specific molecular properties that may be conserved in mammals.

Q3: What are the key mechanisms responsible for the transformation of normal NSC lineage cells into brain tumour-initiation cells?
Cells with NSC-like characteristics exist within brain tumours and can reform whole tumour masses. These so-called brain cancer stem cells are thought to originate from de-differentiation and/or transformation of normal NSC lineage cells. Using a Drosophila brain tumour model, we are screening and characterising genes potentially involved in molecular changes leading to brain tumour initiation and growth. We also use mammalian systems, including human cell cultures and tissues to investigate the role of conserved identified signals.

Prospective students or staff interested in joining our group, please contact Claudia.barros@plymouth.ac.uk.

Available funded posts in our laboratory.

Current lab members

 

Alumni:

  • Dr Karolina Jaworek (PhD 2012–16)
  • Joao Marques (2015–16), Eleni Costa (2015–16) and Oliver Warrington (2014–15) – one-year research undergraduates
  • Eleanor Gonzaga (2013–14) and Helena Robinson (2013–14) – MRes students (Bangor University)
  • Thomas Hughes (2015), Joshua Lewis (2016) and Chelsey Wiley (2017) – MSc students

 

Lab news

Neural stem cell lineages (green) in the Drosophila brain

Publications

  • Xu J, Hartley BJ, Kurup P, Phillips A, Topol A, Xu M, Ononenyi C, Foscue E, Ho S-M & Baguley TD 2016 'Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models' Molecular Psychiatry , DOI PEARL
  • Ding R, Weynans K, Bossing T, Barros CS & Berger C 2016 'The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells' Nature Communications 7, 10510-10510 , DOI PEARL
  • Cahill ME, Jones KA, Rafalovich I, Xie Z, Barros CS, Müller U & Penzes P 2012 'Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition' Mol Psychiatry 17, (1) 1-107 Author Site, DOI PEARL
  • Bossing T, Barros CS, Fischer B, Russell S & Shepherd D 2012 'Disruption of microtubule integrity initiates mitosis during CNS repair' Dev Cell 23, (2) 433-440 Author Site, DOI PEARL
  • Barros CS, Franco SJ & Müller U 2011 'Extracellular matrix: functions in the nervous system' Cold Spring Harb Perspect Biol 3, (1) Author Site, DOI PEARL
  • Barros CS, Nguyen T, Spencer KSR, Nishiyama A, Colognato H & Müller U 2009 'Beta1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth' Development 136, (16) 2717-2724 Author Site , DOI PEARL

  • Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K, Stowers L, Mayford M, Halpain S & Müller U 2009 'Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system' Proc Natl Acad Sci U S A 106, (11) 4507-4512 Author Site, DOI PEARL
  • Radakovits R, Barros CS, Belvindrah R, Patton B & Müller U 2009 'Regulation of radial glial survival by signals from the meninges' J Neurosci 29, (24) 7694-7705 Author Site, DOI PEARL
  • Barros CS, Phelps CB & Brand AH 2003 'Drosophila nonmuscle myosin II promotes the asymmetric segregation of cell fate determinants by cortical exclusion rather than active transport' Dev Cell 5, (6) 829-840 Author Site PEARL
  • Bossing T, Barros CS & Brand AH 2002 'Rapid tissue-specific expression assay in living embryos' Genesis 34, (1-2) 123-126 Author Site, DOI PEARL
  • Van Roessel P, Hayward NM, Barros CS & Brand AH 2002 'Two-color GFP imaging demonstrates cell-autonomy of GAL4-driven RNA interference indrosophila' genesis 34, (1-2) 170-173 , DOI PEARL

Contact Claudia Barros Lab - Neural Stem Cell Research

Plymouth University, Peninsula School of Medicine The John Bull Building, Plymouth Science Park, 16 Research Way, Plymouth PL6 8BU UK