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This Article Full Text Full Text (PDF) All Versions of this Article: 585/3/711    most recent jphysiol.2007.138776v2 jphysiol.2007.138776v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Becker, D. L. Articles by Cook, J. E. Search for Related Content PubMed PubMed Citation Articles by Becker, D. L. Articles by Cook, J. E. Related Collections Cellular

¹ Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK

Neural progenitor cells in the developing retina extend processes that stretch from the basal vitread surface to the apical ventricular surface. During the cell cycle, the nucleus undergoes interkinetic nuclear migration (INM), moving in a vitread direction during G1, passing through S-phase at its peak and then, on entering G2, returning towards the ventricular surface where it enters M-phase and divides. We have previously shown that individual saltatory movements of the nucleus correlate with transient changes in cytosolic calcium concentration within these progenitor cells and that these events spread to neighbouring progenitors through connexin43 (Cx43) gap junction channels, thereby coordinating the migration of coupled clusters of cells. Disrupting coupling with pharmacological agents, Cx43-specific antisense oligodeoxynucleotides (asODNs) or dominant negative Cx43 (dnCx43) inhibits the sharing of calcium events, reducing the number that each cell experiences and significantly slowing INM. We have developed protocols for imaging migrating progenitor cells by confocal microscopy over relatively short periods, and by multiphoton microscopy over more extended periods that include complete cell cycles. We find that perturbing gap junctional communication not only slows the INM of progenitor cells but also apparently prevents them from changing direction at critical phases of the cell cycle. It also disrupts the migration of young neurons to their appropriate layers after terminal division and leads to their ectopic differentiation. The ability to perform extended time-lapse imaging over 3D volumes in living retina using multiphoton microscopy should now allow fundamental mechanisms governing development of the retinal neuroepithelium to be probed in detail.

(Received 16 June 2007; accepted after revision 9 October 2007; first published online 11 October 2007)
Corresponding author D. Becker: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Email: d.becker{at}ucl.ac.uk