Abstract
A recently discovered family of O-manosyltransfearses termed TMTCs was shown to add O-linked mannose to cadherins. TMTC mutations were found to be associated with brain malformations and neurological disorders, suggesting that TMTCs play important roles in the nervous system. However, the biological roles of TMTCs remain poorly understood. TMTCs are well-conserved in animals, from Drosophila to humans, which suggests that Drosophila can serve as a model to elucidate TMTC functions. In this study, we focus on Drosophila TMTC1-3. We found that, during larval stages, TMTC1 and 2 are expressed predominantly in the nervous system, showing broad and prominent expression throughout brain hemispheres and the ventral ganglion. We analyzed mutant phenotypes of these genes, which uncovered that the mutants have a distorted, wave-like pattern of the longitudinal axions. We found that TMTC3 knockout results in similar axonal waving, while the most severe phenotype was detected when RNAi-mediated knockdown was combined with a TMTC3 deficiency. Our data suggest that the TMTC genes have partially redundant functions in the nervous system and potentially regulate Cadherin-N activity. Taken together, our results contribute to elucidating the function of TMTCs in the Drosophila nervous system and have potential implications for uncovering similar mechanisms in humans.
