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The intrinsic specification of γ-aminobutyric acid type A receptor α6 subunit gene expression in cerebellar granule cells

Authors

  • Sabine Bahn,

    1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
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    • * Present address: Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK, and Department of Neurobiology, Babraham Institute, Babraham, Cambridge, CB2 4AT, UK

  • William Wisden,

    1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
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  • Stephen B. Dunnett,

    1. MRC Centre for Brain Repair, Cambridge University Forvie Site, Robinson, Way, Cambridge, CB2 2PY, UK
    2. Department of Experimental Psychology, University of Cambridge, Cambridge, CB2 3EB, UK
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  • Clive Svendsen

    1. MRC Centre for Brain Repair, Cambridge University Forvie Site, Robinson, Way, Cambridge, CB2 2PY, UK
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: Dr William Wisden, as above.
E-mail: ww1@mrc-lmb.cam.ac.uk

Abstract

The patterns of γ-aminobutyric acid type A (GABAA) receptor subunit gene expression in the brain are complex. For example, mouse hippocampal dentate granule cells express many subunit genes, whereas adult cerebellar granule cells, which may share differentiation mechanisms, have a smaller compliment and uniquely express the α6 subunit gene. To see how the α6 expression component arises, i.e. if intrinsically or environmentally specified, we used a mouse line (Δα6lacZ) with a β-galactosidase reporter inserted into the α6 gene. Precursor cells from postnatal day 1 Δα6lacZ cerebellum were transplanted to the adult hippocampus and cerebellum of wild-type mice; 4 weeks after transplantation, Δα6lacZ cells expressed α6-lacZ in the hippocampus, amygdala and cerebellum. Thus, different adult environments support both the development and maintenance of α6 gene expression from cerebellar granule cell precursors. Establishing α6 gene expression is not likely to require specific patterns of neurotransmitter innervation or other factors present only in the developing brain; instead, α6 expression can be timed and maintained autonomously.

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