The BTB-ZF transcription factor Tramtrack69 shapes neural cell lineages by coordinating cell proliferation and cell fate

Cell diversity in multicellular organisms relies on coordination between cell proliferation and the acquisition of cell identity. The equilibrium between these two processes is essential to assure the correct number of determined cells at a given time at a given place. Here, we show that Tramtrack-69 (Ttk69, a BTB-ZF transcription factor ortholog of the human PLZF factor) plays an essential role in controlling this balance. In the Drosophila bristle cell lineage, producing the external sensory organs composed by a neuron and accessory cells, we show that ttk69 loss of function leads to supplementary neural-type cells at the expense of accessory cells. Our data indicate that Ttk69 (1) promotes cell-cycle exit of newborn terminal cells by downregulating cycE , the principal cyclin involved in S-phase entry and (2) regulates cell fate acquisition and terminal differentiation by downregulating the expression of hamlet and upregulating that of Suppressor of Hairless , two transcription factors involved in neural-fate acquisition and accessory-cell differentiation, respectively. Thus, Ttk69 plays a central role in shaping neural cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate commitment. Summary statement Tramtrack-69, a transcription factor orthologous to the human tumor-suppressor PLZF, plays a central role in precursor cell lineages by integrating molecular mechanisms that regulate progenitor cell-cycle exit and cell-fate determination.