Mary Ann Manavalan1, Vatsala Ruvini Jayasinghe1, Rickinder Grewal1, Krishna Moorthi Bhat2. 1. Department of Neuroscience and Cell Biology, University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA. 2. Department of Neuroscience and Cell Biology, University of Texas Medical Branch School of Medicine, Galveston, TX 77555, USA. kmbhat@utmb.edu.
Abstract
Slit proteins act as repulsive axon guidance cues by activating receptors of the Roundabout (Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor. Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion. Moreover, secretion of Slit was required to maintain the fasciculation and position of longitudinal axon tracts, thus maintaining the hardwiring of the nervous system. Thus, Mmy is required for Slit secretion and for maintaining Robo abundance and distribution in the developing nervous system in Drosophila.
Slit proteins act as repulsive axon guidance cues by activating receptors of the pan class="Gene">Roundabout (pan class="Gene">Robo) family. During early neurogenesis in Drosophila melanogaster, Slit prevents the growth cones of longitudinal tract neurons from inappropriately crossing the midline, thus restricting these cells to trajectories parallel to the midline. Slit is expressed in midline glial cells, and Robo is present in longitudinal axon tracts and growth cones. We showed that the enzyme Mummy (Mmy) controlled Slit-Robo signaling through mechanisms that affected both the ligand and the receptor. Mmy was required for the glycosylation of Slit, which was essential for Slit secretion. Mmy was also required for maintaining the abundance and spatial distribution of Robo through an indirect mechanism that was independent of Slit secretion. Moreover, secretion of Slit was required to maintain the fasciculation and position of longitudinal axon tracts, thus maintaining the hardwiring of the nervous system. Thus, Mmy is required for Slit secretion and for maintaining Robo abundance and distribution in the developing nervous system in Drosophila.
Authors: Shawn Cotsworth; Catherine J Jackson; Graham Hallson; Kathleen A Fitzpatrick; Monika Syrzycka; Alistair B Coulthard; Amy Bejsovec; Marcella Marchetti; Sergio Pimpinelli; Simon J H Wang; Robert G Camfield; Esther M Verheyen; Donald A Sinclair; Barry M Honda; Arthur J Hilliker Journal: Cells Date: 2022-01-27 Impact factor: 6.600