UC Riverside

Robust gene expression is crucial for proper embryonic development, and yet it is

subject to extrinsic and intrinsic sources of noise. We investigated mechanisms by which

the C. elegans embryo buffers these stochastic variations in gene expression during

endoderm specification. In this system, the factors that contribute to the specification and

differentiation of the intestine’s progenitor are known, allowing us to probe effects of

upstream stochasticity on known downstream events. The ability of this system to buffer

noise during early embryogenesis was tested by targeting early acting inputs in the

endoderm gene regulatory cascade and measuring its effect on tissue specification and

commitment to differentiate. To study the downstream effects of animals that were on the

verge of not committing to making gut cells and nearly missing endoderm differentiation,

we utilized a series of allelic mutants. These mutant strains specify varied numbers of gut

cells, between 0%-100% of the time. Using these strains, we are currently investigating E

lineage phenotypes during early and mid-embryogenesis, as well as the young adult stage.

We have screened for maternal factors to identify potential modifiers of gut specification,

and showed that specification of endoderm is not an all-or-none event at the level of E

blastomere. Instead, it can be displaced as a binary choice at later time points within the E

lineage – a phenomenon that we are calling "stratified specification". Last, we find that

fully differentiated intestine retains a memory of their “near-miss” specification, which

results in abnormal adult phenotype, due to differential expression of genes in the intestine.

Thus far, we have found that several diverse maternal pathways, including transcription

regulation, metabolism, and apoptosis influence the ability of progeny embryos to make

gut, suggesting that embryonic gene expression is highly sensitive to many sources of

variation. Collectively our data show that gut specification is not an "all-or-none" event,

and that if specification does not occur properly, defects can manifest into adulthood. The

results have implications in other developmental pathways in C. elegans and in any

metazoan system in which gene regulatory networks drive developmentally important

events.