tiK+ toK+: an embryonic clock?
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 pharmacologically 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 development. 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 chromosomal cycle and may represent a distinct oscillatory timing activity with possible developmental significance.
Day
M L
ML
Department of Physiology, University of Sydney, NSW, Australia.
Winston
N
N
McConnell
J L
JL
Cook
D
D
Johnson
M H
MH
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D015221:Potassium Channels / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D013997:Time Factors; D015053:Zygote / Q000502:physiology
D015221:Potassium Channels