Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells.
During early retinal development, progenitor cells must divide repeatedly to expand the progenitor pool. During G(1) and G(2) of the cell cycle, progenitor cell nuclei migrate back-and-forth across the proliferative zone in a process termed interkinetic nuclear movement. Because division can only occur at the ventricular surface, factors that affect the speed of nuclear movement could modulate the duration of the cell cycle. Gap-junctional coupling and gap junction-dependent Ca(2+) activity are common features of proliferating cells in the immature nervous system. Furthermore, both gap-junctional coupling and changes in [Ca(2+)](i) have been shown to be positively correlated with the migration of a number of immature cell types. Using time-lapse confocal microscopy, we describe the nature and rate of progenitor cell interkinetic nuclear movement. We show that nuclear movement is usually, but not always, associated with Ca(2+) transients and that buffering of these transients with BAPTA slows movement. Furthermore, we show for the first time that gap-junctional communication is an important requirement for the maintenance of normal nuclear movement in retinal progenitor cells. Conventional blockers of gap junctions and transfection of cells with dominant-negative constructs of connexin 43 (Cx43) and Cx43-specific antisense oligodeoxynucleotides (asODNs) all act to slow interkinetic nuclear movement. The gap junction mimetic peptide Gap26 also acts to slow movement, an effect that we show may be attributable to the blockade of gap junction hemichannels.
Pearson
Rachael A
RA
Department of Physiology, University College London, London WC1E 6BT, United Kingdom. rachael.pearson@ich.ucl.ac.uk
Lüneborg
Nanna L
NL
Becker
David L
DL
Mobbs
Peter
P
D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D002642:Chick Embryo; D017629:Gap Junctions / Q000502:physiology*; D012160:Retina / Q000166:cytology* / Q000196:embryology / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*