The decision between proliferation and invasive differentiation is a key part of several developmental events as well as cancer; however, how cells switch between these states is not well understood. Two cell types in the C. elegans somatic gonad, the anchor cell (AC) and ventral uterine (VU) cells, both specified from initially equipotent cells through a Notch-mediated cell fate decision, serve as an excellent model of this dichotomy in cellular behavior. The post-mitotic AC, the default state of the AC/VU decision, goes on to invade the underlying basement membrane during development of the reproductive system, while the VUs remain proliferative. We have previously shown that four transcription factors,
fos-1 (Fos),
egl-43 (EVI1/MEL),
hlh-2 (E/Daughterless), and
nhr-67 (NR2E1/Tailless/TLX), are necessary for AC invasion, with the latter three playing a role in regulating cell cycle arrest. We next examined whether any of these transcription factors are sufficient for invasion and find that ectopic expression of NHR-67, which is enriched in the AC compared to its neighbors, results in transdifferentiation of VUs into invasive ACs. We hypothesize that post-translational degradation of HLH-2 in the VU results in lower levels of NHR-67 and that a transcriptional repressive mechanism functions in the VU to prevent remaining NHR-67 activity from inappropriately activating AC-specific targets. We find that knockdown of
unc-37 and
lsy-22, homologs of the transcriptional repressor Groucho, results in a low penetrance of animals with multiple ACs. Others have previously demonstrated that Groucho forms a repressive complex with histone deacetylase (
hda-1) and TCF/LEF (
pop-1) to restrict endoderm differentiation in the early embryo. Unlike
hda-1 or Groucho, which are not differentially expressed between the two cell types,
pop-1 is enriched in the VUs compared to the AC, but does not appear to activate transcription based on quantification of a transgenic POP-1 activity reporter. Furthermore, we find that depletion of the pro-invasive TFs associated with cell cycle arrest results in ectopic expression of
pop-1 in the AC. Here, we investigate whether differential
pop-1 levels are necessary for AC/VU fate maintenance as well as whether this process is downstream or synergistic with Notch signaling and/or cell cycle dynamics. Together, these results provide new insights into how cells can establish and maintain cellular programs necessary for growth and morphogenesis.