Biological systems are inherently subject to sources of intrinsic and extrinsic noise. Intrinsic noise includes things such as variation in the number of transcripts made for a particular gene product, while extrinsic noise includes variation in environmental resources or temperature. Despite these sources of noise, development of C. elegans is highly robust and occurs reproducibly well in nearly 100% of embryos.
By introducing single copies of the endoderm-specifying end genes into strains lacking the original end-1 and end-3 genes (see the description of the network), we have found that mutation of the MED binding sites causes endoderm specification to become highly stochastic. In the example above, genetically identical embryos -- each homozygous for null mutations in end-1 and end-3, and homozygous for a single-copy insertion of an end-1 gene lacking MED binding sites -- occasionally make gut (white granules) but usually do not. Even those animals that make gut nonetheless have defects in gut cell number, and those animals that survive to adulthood have many other defects. These results suggest that even if gut progenitors are correctly specified to an endoderm fate, the intestine does not always develop normally. Our current results suggest that surviving adults have defects in metabolism.
Paper showing MED-1,2 promote robustness of gut specification: Maduro et al. (2015)
Review on robustness in the C. elegans embryo: Maduro (2015)
Stochastic effects of partial specification on gut development: Choi et al. (2017)
