The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors in distinct cholinergic and serotonergic neuron types.

14 páginas, 8 figuras, 1 tabla. Material suplementario accesible online.Transcription factors that drive neuron type-specific terminal differentiation programs in the developing nervous system are often expressed in several distinct neuronal cell types, but to what extent they have similar or distinct activities in individual neuronal cell types is generally not well explored. We investigate this problem using, as a starting point, the C. elegans LIM homeodomain transcription factor ttx-3, which acts as a terminal selector to drive the terminal differentiation program of the cholinergic AIY interneuron class. Using a panel of different terminal differentiation markers, including neurotransmitter synthesizing enzymes, neurotransmitter receptors and neuropeptides, we show that ttx-3 also controls the terminal differentiation program of two additional, distinct neuron types, namely the cholinergic AIA interneurons and the serotonergic NSM neurons. We show that the type of differentiation program that is controlled by ttx-3 in different neuron types is specified by a distinct set of collaborating transcription factors. One of the collaborating transcription factors is the POU homeobox gene unc-86, which collaborates with ttx-3 to determine the identity of the serotonergic NSM neurons. unc-86 in turn operates independently of ttx-3 in the anterior ganglion where it collaborates with the ARID-type transcription factor cfi-1 to determine the cholinergic identity of the IL2 sensory and URA motor neurons. In conclusion, transcription factors operate as terminal selectors in distinct combinations in different neuron types, defining neuron type-specific identity features.This work was funded by the National Institutes of Health [R01NS039996-05 and R01NS050266-03 to O.H.; R01NS076558 to D.A.C.-R.; and R01NS070644 to R.S.M.]; a March of Dimes Foundation Grant (to D.A.C.-R.); the Spanish Government [SAF2011-26273 to N.F.]; a Marie Curie Career Integration Grant (to N.F.); a VAL i+d Fellowship from Generalitat Valenciana (to C.L.-F.); and a European Research Council Starting Grant (to N.F.). N.F. is a National Alliance for Research on Schizophrenia and Depression (NARSAD) Young Investigator. O.H. is an Investigator of the Howard Hughes Medical Institute. Deposited in PMC for release after 6 months.Peer reviewe