Past research: Transcription factor control of vulval development
The C. elegans vulva is a paradigm of organogenesis and involves a combination of EGF-Ras and Notch signaling, cell migrations, remodelling of adherens junctions, cell fusions, muscle attachments and invariant cell divisions. For a great overview of vulval development, see this WormBook article. We have previously examined how a single regulatory input, sumoylation, differentially modulates the activity of a conserved C. elegans nuclear hormone receptor, NHR-25, in different cell types (Ward et al., 2013). Using a combination of yeast-two hybrid analyses, in vitro biochemistry, genetics and imaging, we revealed that NHR-25 is sumoylated, and this modification was critical for restraining NHR-25 activity to faithfully promote/maintain cell-fate during development. We are now exploring: i) how does NHR-25 sumoylation regulate cell-fate during vulval development; ii) what is the upstream signaling pathway regulating NHR-25 sumoylation; and iii) how sumoylation regulates NHR-25 activity in different tissues during development? This project will reveal how gene regulation from transcription factors is converted into specific cellular behaviors and how transcription factors integrate signals during animal development to temporally and spatially control gene expression.
An NHR-25 activity reporter (8xNR5RE:(WT)::NLS::3xVenus) is undetectable (i-ii) until sumo is depleted (smo-1(RNAi)) (iii-vii), upon which it becomes expressed in each tissue in which NHR-25 is known to be active. From Ward et al., 2013.