Molecular clocks in development

During the formation of an embryo, the events that lead to determination of the various cell types seem to be controlled by developmental timers which operate within individual cells. A remarkable example of this timekeeping is provided by the transition from rapid and symmetrical cell divisions to slow and asymmetrical divisions in embryos of the toad Xenopus laevis. This transition always occurs at the twelfth cleavage after fertilization, when the embryo consists of just over 2,000 cells known as blastomeres. The timing of the transition is controlled by a clock that is intrinsic to each blastomere — timing does not depend on cell-cell interactions³³. Another example comes from precursor cells that differentiate to form oligodendrocytes, a type of non-neuronal cell found in the vertebrate nervous system. When placed individually in single wells, these precursors divide a number of times before differentiating. Two daughter cells from the same precursor undergo a synchronized number of divisions, and differentiate at the same time³⁴.

Developmental clocks such as these are probably distinct from those that govern circadian rhythms, although the molecular mechanisms that control proliferation and differentiation programmes are obviously intermingled with cellular oscillatory functions. For example, expression of the avian equivalent of the Drosophila gene hairy in the chick is controlled by a molecular clock that is linked to the formation of somites. Hairy is expressed in cyclic pulses with a periodicity of 90 minutes — exactly the time that it takes to form one somite. Movement of the pulses does not depend on cell displacement or on propagation of an activating signal, and each cell seems to have its own functional clock³⁵.

Because of its intrinsic free-running property, the cell division cycle must also be considered as a molecular clock. Most eukaryotic cells in culture undergo mitosis (nuclear division) with a periodicity of roughly 24 hours. Is this just coincidence, or were cells sensitive to light-dark cycles millions of years ago? If they were, what we study today as the cell cycle could represent a vestigial circadian rhythm.