Abstract
Terminal differentiation generates the specialized structures and functions that allow postmitotic cells to acquire their distinguishing characteristics. This process is thought to be controlled by transcription factors called “terminal selectors” that directly activate a set of effector genes. Using the mechanosensory touch receptor neurons (TRNs) in Caenorhabditis elegans, we extend this concept by identifying the ZEB family transcriptional repressor ZAG-1 as a non-selector regulator of cell fate. ZAG-1 does not activate TRN genes directly but promotes TRN differentiation by preventing the expression of the TEA domain transcription factor EGL-44 and its binding partner EGL-46, which are potent repressors of TRN fate. The EGL-44/EGL-46 complex normally blocks the activation of TRN genes by the terminal selectors, UNC-86 and MEC-3, in the multidendritic nociceptor FLP neurons, whose fate also requires UNC-86 and MEC-3. Thus, TRN and FLP neurons share the same terminal selectors and a common ground state. Diversification beyond this ground state is controlled by ZAG-1 and EGL-44, which form a negative feedback loop through the reciprocal inhibition to regulate the choice between the two neuronal fates.
Summary statement Transcriptional repressors regulate binary fate choices through reciprocal inhibition during terminal neuronal differentiation. Specifically, ZEB family transcription factor indirectly promotes fate specification of sensory neuron by inhibiting TEA domain-containing repressor.
