Neuronal Synaptic Outputs Determine the Sexual Fate of Postsynaptic Targets

Synapses mediate inductive interactions for the proper development of pre- and postsynaptic cells: presynaptic electrical activities and synaptic transmission ensure the organization of postsynaptic structures, whereas neurotrophins produced in postsynaptic cells support the survival and enlargement of presynaptic partners [1]. In Drosophila, a motor nerve has been implicated in the induction of the muscle of Lawrence (MOL) [2-4], the formation of which is male specific and depends on the neural expression of fruitless (fru) [5, 6], a neural sex-determinant gene [7, 8]. Here we report the identification of a single motoneuron essential for inducing the MOL, which we call the MOL-inducing (Mind) motoneuron. The MOL is restored in fru mutant males, which otherwise lack the MOL, if the fru⁺ transgene is selectively expressed in the Mind motoneuron by mosaic analysis with a repressible cell marker [9]. We further demonstrate that synaptic outputs from the Mind motoneuron are indispensable to MOL induction, because the blockage of synaptic transmission by shibire^ts (shi^ts) during the critical period in development abolished the MOL formation in males. Our finding that sex-specific neurons instruct sexually dimorphic development of their innervating targets through synaptic interactions points to the novel mechanism whereby the pre- and postsynaptic partners coordinately establish their sexual identity.