The Molecular Biology of Cell Determination and Cell Differentiation

L D Etkin, Etkin, L D, Etkin, Laurence D., Laurence D. Etkin

The cleavage cycles during early amphibian development are synchronous, rapid, and biphasic. There is no transcription and no growth of the embryo, and the nuclear cycle is independent of the cytoplasmic cleavage cycle. All components necessary for development through the blastula stage are provided by maternal stores. At the twelfth cleavage division, a major transition occurs that involves initiation of transcription, an elongation of the cell cycle, an increase in cell movement, and asynchrony of cell division. It is probable that the major controlling factor in the regulation of all the aforementioned events is the cell cycle. During early cleavage stages, the cell cycle is both rapid (30-35 min) and synchronous. There is evidence that the cycling time may be controlled by the presence of several mitotic factors, such as MPF, CSF (cytostatic factor), and a titratable component that binds to nuclear membranes. The rapid rate of DNA synthesis may inhibit the formation of transcription complexes, resulting in the absence of detectable transcription before the MBT. Cellular movement may also be inhibited in the rapidly dividing cell. As the cell cycle elongates (possibly due to the functional loss or sequestration of one or more of the mitotic control factors), the G1 and G2 phases are incorporated into the cell cycle. Under conditions of slower rates of DNA replication and the presence of the G1 and G2 phases, the transcriptional machinery becomes functional. It is apparent that at the MBT, not all classes of transcripts are activated simultaneously in every cell, nor is their expression regulated by a common mechanism. Incorporation of the G1 and G2 phases in the cell cycle may also permit the synthesis and assembly of microtubules and cytoskeletal components necessary for the initiation of the cell movements characteristic of this stage of development. The role of the cell cycle in controlling events at the MBT is supported by evidence from studies in which perturbation of the cell cycle that results in its elongation or arrest produces subsequent initiation of events that occur normally at the MBT. The MBT therefore appears to be a window in the developmental time frame, during which a number of molecular and morphogenetic events occur independently of one another, but all are necessary for subsequent morphogenesis and cellular differentiation. It is a transition from the strict reliance on the maternal program to a dependence on the new transcription from the embryonic genetic program. It is probable that the major regulatory mechanism involved in the occurrence of this constellation of cellular events is the change in the cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS)