71.4 Saturday, Jan. 5 Patterning of cell cycle arrest during formation of the nematode uterine-vulval connection MATUS, D.Q.*; CHANG, E.; SHERWOOD, D.R.; Duke University email@example.com
During development, transcription factors program the differentiation of discrete cell types. The adoption of a differentiated fate is often accompanied by cell cycle arrest. Many of these differentiated cells are then required to execute morphogenetic behaviors. Data suggests that the complex cell biological behaviors that occur during morphogenesis (e.g., EMT and convergent extension) also require a prolonged cell cycle arrest. We are examining the transcriptional control of cell cycle arrest during nematode larval development. The anchor cell (AC), a specialized gonadal cell, invades through the underlying basement membranes (BM) to connect the developing uterine and vulval tissues. After initiating the breach, the AC is no longer required to expand the BM gap. Instead, the BM breach is widened through BM sliding and is stabilized by the innermost secondary fated vulval precursor cell, vulD. We are dissecting AC invasion and vulval morphogenesis in C. elegans and related nematode species as a model to understand how morphogenetic mechanisms evolve. We performed a tissue-specific RNAi screen targeting ~700 C. elegans transcription factors, identifying the TLX ortholog NHR-67 as a new regulator of invasion. Strikingly, loss of NHR-67 results in multiple mitotic ACs that fail to invade. Prevention of cell cycle progression in NHR-67-depleted animals rescues the invasion defect, demonstrating that cell cycle arrest is required for invasion. This requirement for cell cycle arrest may also hold true during BM stabilization. Similar to C. elegans, in all other nematode species we have examined, the BM appears stabilized over the post-mitotic vulD cell. Together our molecular, cell biological, developmental and evolutionary studies indicate a requirement for the precise transcriptional control of a genetic program that links cell cycle arrest to both BM invasion and stabilization.