Development, the process by which a single cell multiplies and differentiates into a multicellular organism, can be thought of as an intricate program encoded within our DNA that is executed by the process of gene expression. In order to measure gene expression directly in its cellular context, we have developed a method for detecting RNA via fluorescence microscopy, revealing each molecule as a fluorescent spot. By using this method to quantify absolute numbers of RNA in individual cells, we found that gene expression can be a remarkably noisy process in animal cells, and yet the developmental process remains remarkably robust despite all these fluctuations. We explored the consequences of variability in the context of intestinal development in the nematode C. elegans. We found that the natural network exhibits very low fluctuations, but perturbations to the networks can reveal extensive hidden noise that leads to variability in cell fate. This finding provides a mechanism for the oft-observed genetic phenomenon of the incomplete penetrance of mutant phentoypes.
