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Thursday 30 May at 1pm
Proliferation, migration and differentiation of neuronal stem cells
David Becker, Jeremy Cook and Regina Nickel
The vertebrate nervous system, with its millions of nerve cells and support cells, is built from a thin, rolled sheet of self-replicating precursor cells (neuronal stem cells) called a neuroepithelium. In the early embryo, the neuroepithelial cells are packed together in a single layer but the cell cycle is tightly linked to migrations of the cell body (perikaryon) called interkinetic nuclear movements, which bring the neuronal precursors into the closest possible contact with others that are in the same cell-cycle phase while they are making their fate choices. Each cell mainly contacts dividing neighbours while it is dividing, and DNA-replicating neighbours while it is replicating its own DNA.
Using real-time imaging of chick retinal organ cultures, we have recently shown that interkinetic nuclear movements are built from small, intermittent steps that match individual transient intracellular calcium events and are synchronized across local cell clusters. Their frequency is enhanced both by gap junctional communication and by paracrine ATP signalling through gap-junctional hemichannels.
This population-coordinated mitotic and migratory behaviour raises the exciting possibility that connexin-based communication might be a valuable target for experimental and therapeutic intervention in the mechanisms that control the numbers and positions of neurons, determine their functional types and organize them into circuits that process information.
We have laid experimental plans that we hope will allow us to unravel the overlapping effects of the junctional and paracrine pathways on cell shape, cycle progression, cycle re-entry and exit, migration and differentiation. The migratory and differentiative responses, in particular, will be followed by multiphoton microscopy over a mitotic cycle or more, using eGFP-tagged proteins, vital stains and the excellent technical facilities of the Centre for Cell and Molecular Dynamics in which we are situated.
This work is funded by the BBSRC
With thanks also to Viola Bonness, Marina Catsicas, Nanna Lüneborg and Rachael Pearson, all formerly in the lab of Prof Peter Mobbs (UCL Physiology), and to Kevin Webb, formerly in our own lab.
Related articles and links
- Cook, J.E. and Becker, D.L. (2009) Gap junction proteins in retinal development: new roles for the 'nexus'. Physiology 24, 219-230.
- Becker, D.L., Webb, K.F., Thrasivoulou, C., Lin, C.-C., Nadershahi, R., Tsakiri, N. and Cook, J.E. (2007) Multiphoton imaging of chick retinal development in relation to gap junctional communication. J. Physiol. 585, 711-719.
- Pearson, R.A., Lüneborg, N.L., Becker, D.L. and Mobbs, P. (2006) Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells. J. Neuroscience 25, 10803-10814.
- Pearson, R.A., Catsicas, M., Becker, D.L., Bayley, P., Lüneborg, N. and Mobbs, P. (2004) Ca2+ signalling and gap junction coupling within and between pigment epithelium and neural retina in the developing chick. European J. Neurosci. 19, 2435-2445.
- Becker, D.L., Ciantar, D., Catsicas, M., Pearson, R.A. and Mobbs, P. (2002) Use of pIRES vectors to express eGFP and connexin constructs in studies of the role of gap junctional communication in the early development of the chick retina and brain. Cell Communication and Adhesion 8, 355-359.
- Pearson, R.A., Catsicas, M., Becker, D.L. and Mobbs, P. (2002) Purinergic and muscarinic modulation of the cell cycle and calcium signaling in the chick retinal ventricular zone. J. Neurosci. 22, 7569-7579.
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