Ciliary transition zone activation of phospho-Tctex-1 controls ciliary resorption, S-phase entry and fate of neural progenitors

Primary cilia are displayed during the G(0)/G(1) phase of many cell types. Cilia are reabsorbed as cells prepare to re-enter the cell cycle, but the causal and molecular link between these two cellular events remains unclear. We show that phospho(T94)Tctex-1 is recruited to ciliary transition zones prior to S-phase entry and plays a pivotal role in both ciliary disassembly and cell cycle progression. Tctex-1’s role in S-phase entry, however, is dispensable in non-ciliated cells. Exogenously added phosphomimic Tctex-1 T94E accelerates cilium disassembly and S-phase entry. These results support a model in which the cilia act as a brake to prevent cell cycle progression. Mechanistic studies show the involvement of actin dynamics in Tctex-1 regulated cilium resorption. Phospho(T94)Tctex-1 is also selectively enriched at the ciliary transition zones of cortical neural progenitors, and plays a key role in controlling G(1) length, cell cycle entry, and fate determination of these cells during corticogenesis.