Abstract
Neurogenesis is achieved through a sequence of steps that include specification and differentiation of progenitors into mature neurons. Frequently, precursors migrate to distinct positions before terminal differentiation. The Slit-Robo pathway, formed by the secreted ligand Slit and its membrane bound receptor Robo, was first discovered as a regulator of axonal growth. However, today, it is accepted that this pathway can regulate different cellular processes even outside the nervous system. Since most of the studies performed in the nervous system have been focused on axonal and dendritic growth, it is less clear how versatile is this signaling pathway in the developing nervous system. Here we describe the participation of the Slit-Robo pathway in the development of motion sensitive neurons of the Drosophila visual system. We show that Slit and Robo receptors are expressed in different stages during the neurogenesis of motion sensitive neurons. Furthermore, we find that Slit and Robo regulate multiple aspects of their development including neuronal precursor migration, cell segregation between neural stem cells and daughter cells and formation of their connectivity pattern. Specifically, loss of function of slit or robo receptors in differentiated motion sensitive neurons impairs dendritic targeting, while knocking down robo receptors in migratory progenitors or neural stem cells leads to structural defects in the adult optic lobe neuropil, caused by migration and cell segregation defects during larval development. Thus, our work reveals the co-option of the Slit-Robo signaling pathway in distinct developmental stages of a neural lineage.
Highlights
The development of every tissue is orchestrated in a sequence of discrete steps
In brains from slidui/ + animals, we found occasional mistargeting of T4 projections, in slidui mutants, T4 neurons overgrew to distal layers of the medulla in all scored animals and these ectopic projections were substantially thicker and probably reflecting axonal fasciculation (Figures 1C–F). These results indicate that Slit protein is necessary for the correct development of the lobula plate and T4 neurons in particular, it is unclear whether these defects are a direct result of the lack of Slit acting on Robo receptors in the lobula plate or a consequence of the role of Slit in medulla development
We found that Robo1 and Robo2 are differentially expressed along the inner proliferating center (IPC); low expression is observed in the p-IPC neuroepithelium, while high expression is observed in migratory progenitors (Figures 2A–B, see intensity quantifications in Supplementary Figure 1)
Summary
The development of every tissue is orchestrated in a sequence of discrete steps. Strikingly, a small repertoire of signaling pathways, which are co-opted throughout development, regulate the formation of tissues and organs. Several signaling pathways involved in distinct steps of the differentiation of neurons of the motion detection system have been identified in the past few years (Apitz and Salecker, 2018; Mora et al, 2018; Pinto-Teixeira et al, 2018). In Drosophila and vertebrates, the ligand Slit binds to different Robo receptors that regulate axon pathfinding decisions during development. In this context, Robo triggers a molecular cascade that modulates cytoskeleton behavior leading in most cases to neurite retraction (Dickson and Gilestro, 2006). We propose that during lobula plate development, the Slit-Robo signaling acts in every step from neuronal precursor migration to neuronal wiring
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
