Aspects of the molecular regulation of early mammalian development.

Many regulatory systems operate in the early mammalian embryo. This brief overview surveys several systems and their integration including polarities and axes, left-right differentiation, timers in cells, tissues and in gene expression, and imprinting. Polarities are essential from the very earliest stages of oocyte formation, and maintain their significance until blastocyst stages and beyond. They determine cleavage axes and the distribution of maternal proteins in the oocyte, distinct distributions being identified at the animal pole especially. Left-right axes are no doubt expressed from the earliest embryonic stages, and perhaps even in determining slight differences in the axes of cleavage and of maternal protein distribution. Timers, equally fundamental, have been demonstrated to control many functions in oocytes and embryos. Many fundamental processes in early mammalian oocytes and embryos are closely timed. They are classified into circadian rhythms, hourglass timers, clocks regulating major aspects of development including transcription, longevity via telomere clocks and long-range systems. Imprinting and methylation, increasingly important in establishing stable phenotypes in early embryos, might develop abnormally under some circumstances including intracytoplasmic sperm injection and cloning. A general summary briefly describes some other aspects of regulation, especially chromosomal anomalies in human embryos.