tiK+ toK+: an embryonic clock?

Abstract

During embryogenesis cells make appropriately timed developmental decisions. Both ‘hourglass-like’ and ‘clock-like’ mechanisms have been demonstrated to act as timers in early development. The cell cycle rhythm, using feedback circuits to drive cells unidirectionally through checkpoints, is an example of a clock-like timer, but how it operates to time developmental events is unclear. In other cell types, cyclic oscillations in K⁺ channel activity, which parallel cell cycle and circadian rhythms, may be part of the timing mechanism. Changes in K⁺ oscillations accompany key developmental transitions and oncogenic transformation. Channel blockade interferes pharmaco-logically with cell cycle initiation or progression, whereas channel over-expression can be oncogenic. K⁺ channel activity also exists in early mouse oocytes through to at least the blastocyst stage, and it oscillates in phase with the developmental cell cycles, being high in M/G₁ and low in S/G₂. It resembles physiologically the activity of the K⁺ channels of the eag- or erg-like families. Reverse transcriptase–polymerase chain reaction of mouse oocytes has revealed the presence of transcripts encoding both EAG- and ERG-like proteins throughout preimplantation devel-opment. Channel activity continues to oscillate with a cell cycle periodicity in embryos from which the nucleus has been removed, or after inhibition by puromycin of the cyclin B–cyclin-dependent kinase 1 driven component of the chromosomal cycle. Channel oscillatory activity thus appears to be able to function autonomously of the chromo-somal cycle and may represent a distinct oscillatory timing activity with possible developmental significance.