A novel member of the Ig superfamily, turtle, is a CNS-specific protein required for coordinated motor control

We describe here the cloning and functional characterization of a neural-specific novel member of the Ig superfamily, turtle (tutl), with a structure of five Ig C2-type domains, two fibronectin type III domains, and one transmembrane region. Alternative splicing of the tutl gene produces at least four Tutl isoforms, including two transmembrane proteins and two secreted proteins, with primary structures closely related to a human brain protein (KIAA1355), the Deleted in Colorectal Cancer/Neogenin/Frazzled receptor family, and the Roundabout/Dutt1 receptor family. An allelic series of tutl gene mutations resulted in recessive lethality to semilethality, indicating that the gene is essential. In contrast to other family members, tutl does not play a detectable role in axon pathfinding or nervous system morphogenesis. Likewise, basal synaptic transmission and locomotory movement are unaffected. However, tutl mutations cause striking movement defects exhibited in specific types of highly coordinated behavior. Specifically, tutl mutants display an abnormal response to tactile stimulation, the inability to regain an upright position from an inverted position (hence, "turtle"), and the inability to fly in adulthood. These phenotypes demonstrate that tutl plays an essential role in establishing a nervous system capable of executing coordinated motor output in complex behaviors.