Heterochronic Genes and the Nature of Developmental Time

Timing is a fundamental issue in development, with a range of implications from birth defects to evolution. In the roundworm Caenorhabditis elegans, the heterochronic genes encode components of a molecular developmental timing mechanism. This mechanism functions in diverse cell types throughout the animal to specify cell fates at each larval stage. MicroRNAs play an important role in this mechanism by stage-specifically repressing cell-fate regulators. Recent studies reveal the surprising complexity surrounding this regulation — for example, a positive feedback loop may make the regulation more robust, and certain components of the mechanism are expressed in brief periods at each stage. Other factors reveal the potential for important roles of steroid hormones and targeted proteolysis. Investigation of the heterochronic genes has revealed a mechanism composed of precisely timed switches linked to discrete developmental stages. Timing is a dimension of developmental regulation that may be difficult to witness in vertebrates because developmental stages are not as discrete as in C. elegans, each tissue is likely to be independently regulated. Homologs of certain heterochronic genes of vertebrates show temporally regulated expression patterns, and may ultimately reveal timing mechanisms not previously known to exist.