Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States
Rebecca C Stecky
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States
Lauren Neal
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States
Phinikoula S Katsamba
Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, United States
Goran Ahlsen
Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, United States
Vishnu Balaji
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Thorsten Hoppe
Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, United States
Sex-specific synaptic connectivity is beginning to emerge as a remarkable, but little explored feature of animal brains. We describe here a novel mechanism that promotes sexually dimorphic neuronal function and synaptic connectivity in the nervous system of the nematode Caenorhabditis elegans. We demonstrate that a phylogenetically conserved, but previously uncharacterized Doublesex/Mab-3 related transcription factor (DMRT), dmd-4, is expressed in two classes of sex-shared phasmid neurons specifically in hermaphrodites but not in males. We find dmd-4 to promote hermaphrodite-specific synaptic connectivity and neuronal function of phasmid sensory neurons. Sex-specificity of DMD-4 function is conferred by a novel mode of posttranslational regulation that involves sex-specific protein stabilization through ubiquitin binding to a phylogenetically conserved but previously unstudied protein domain, the DMA domain. A human DMRT homolog of DMD-4 is controlled in a similar manner, indicating that our findings may have implications for the control of sexual differentiation in other animals as well.
