Evolution of Endomesoderm Specification

In C. elegans, loss of maternal function of the gene Ce-pop-1 results in a transformation of the MS cell into an E-like cell, causing developmental arrest with an excess of endoderm (gut; Figs. A,B at right). We have found that in the related nematode C. briggsae, depletion of the pop-1 ortholog causes loss of gut (Figs. C,D). This surprising result is actually the 'reverse' of the C. elegans phenotype: Laser ablation studies, in which all cells except E are killed, suggest that E adopts the fate of MS in C. briggsae pop-1(RNAi) embryos.

end3inSitu We have found that the basis for this difference in pop-1 phenotypes correlates with the way that POP-1 contributes to proper end gene activation in the two species. In both, the end genes are activated in E. In C. elegans, loss of POP-1 results in de-repression of the end genes in the MS cell (and a decrease in their activation overall; Figs A,B on the left), while in C. briggsae, there is complete loss of end expression with Cb-pop-1(RNAi) (Figs C,D).
We have also observed that Cb-skn-1(RNAi) results in persistence of MS-derived pharynx, while loss of both Cb-pop-1 and Cb-skn-1 through RNAi results in loss of MS fate. These results show that the regulatory logic of the combined input of the SKN-1 and POP-1 pathways is different in the two species: In C. elegans, SKN-1 specifies MS and E fates, with POP-1 repressing E fate in MS, and contributing to activation of E fate in E; In C. briggsae, SKN-1 and POP-1 provide an 'OR' input into MS fate (with no evidence that POP-1 represses E fate in MS), and an 'AND' input for E fate. Hence, regulation by these factors can be integrated in more than one way to produce the same output.
networks Cb, Ce

Other current projects include trying to understand the molecular basis for the differences in phenotypes, and examination of this network in other species related to C. elegans and C. briggsae. Most recently we published a paper that predicts the orthologs of the MED and END factors in the closest relatives of C. elegans:

MEDs and ENDs

Evolution of med factors in C. remanei, C. briggsae and C. elegans: arrowCoroian et al. (2006)
Different phenotypes of pop-1 and skn-1 knockdown in C. briggsae:  arrow
Lin et al. (2009)
Paper on orthologues of MED and END genes: arrowMaduro (2020)
Evolution of GATA factors in nematodes: arrowEurmsirilerd & Maduro (2020)