EGF, WNT & HOX Interactions during Patterning of Caenorhabditis elegans Equivalence Groups

Citation

Seah, Adeline (2009) EGF, WNT & HOX Interactions during Patterning of Caenorhabditis elegans Equivalence Groups. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/N559-AE78. https://resolver.caltech.edu/CaltechETD:etd-05242009-123432

Abstract

During development, as a single-cell zygote divides multiple times to generate a complete organism, previously undifferentiated cells somehow acquire the correct fates. A group of cells that shares the same developmental potential is called an equivalence group. In Caenorhabditis elegans, the most well-characterized equivalence group is the hermaphroditic Vulval Precursor Cell (VPC) group. Epidermal Growth Factor (EGF) signaling specifies VPC fate partly by upregulation of lin-39/SexcombsReduced/Hox5, while Wnt signaling plays a minor role in vulval induction. EGF and Wnt signaling also act together to pattern the P11/12 equivalence group, present in both C. elegans hermaphrodites and males, by upregulating a different Hox gene, egl-5/Antennapedia/Ultrabithorax/Hox6/8, to specify P12 fate. Previous observations suggest that EGF or Wnt signaling may act through Hox genes to specify fate in two other C. elegans equivalence groups: the Hook Competence Group (HCG) and γ/δ pair. I characterized the roles of EGF and Wnt signaling in the HCG and γ/δ pair and found that upregulation of Hox genes is controlled by either pathway in each group.

I showed that the major hook inductive pathway involves the Wnt ligands and LIN-17/Fz, which specify the 1° and 2° HCG fates. Also, I identified a role for EGF signaling in specifying the 1° fate, although its role is only revealed when Wnt activity is compromised. I provided a link between mab-5/Hox6/8 and Wnt signaling during normal hook development by determining that LIN-17 is required for mab-5/Hox6/8 expression in P11.p.

In the γ/δ pair, I demonstrated that EGF signaling (through the LIN-31/Forkhead and LIN-1/ETS transcription factors) controls ceh-13/Hox1 expression in γ. I did not find any evidence that Wnt signaling specifies the γ fate. Instead, I observed that lin-44/Wnt, mom-2/Wnt and lin-17/Fz are required to orient the γ mitotic spindle. In addition, TGF-β signaling (by dbl-1/Dpp) was previously reported to control γ expression of ceh-13/Hox1. I showed that dbl-1 acts either downstream or in parallel to EGF signaling to specify the γ fate. I also found that dbl-1/Dpp does not appear to specify fates in the VPC and P11/12 equivalence groups, in which EGF signaling plays an important role, suggesting that TGF-β signaling contributes to the specificity of the γ fate.

Thesis Files