Expression of netrin and its receptors uncoordinated‐5 and frazzled in arthropods and onychophorans suggests conserved and diverged functions in neuronal pathfinding and synaptogenesis

Abstract

Background: Development of the nervous system and the correct connection of nerve cells require coordinated axonal pathfinding through an extracellular matrix. Outgrowing axons exhibit directional growth toward or away from external guidance cues such as Netrin. Guidance cues can be detected by growth cones that are located at the end of growing axons through membranebound receptors such as Uncoordianted-5 and Frazzled. Binding of Netrin causes reformation of the cytoskeleton and growth of the axon toward (or away from) the source of Netrin production.Results: Here, we investigate the embryonic mRNA expression patterns of netrin genes and their potential receptors, uncoordinated-5 and frazzled in arthropod species that cover all main branches of Arthropoda, that is, Pancrustacea, Myriapoda, and Chelicerata. We also studied the expression patterns in a closely related outgroup species, the onychophoran Euperipatoides kanangrensis, and provide data on expression profiles of these genes in larval tissues of the fly Drosophila melanogaster including the brain and the imaginal disks. Conclusion: Our data reveal conserved and diverged aspects of neuronal guidance in Drosophila with respect to the other investigated species and suggest a conserved function in nervous system patterning of the developing appendages.

Review of extra-embryonic tissues in the closest arthropod relatives, onychophorans and tardigrades

“…Modifications of the dorsal extra-embryonic tissue in yolk-free embryos and the expression of gut marker genes in the ventral extra-embryonic tissue of the lecithotrophic species suggest a role in nutrient uptake and gut development. Moreover, cytological and gene expression data indicate an involvement of extra-embryonic tissues in other developmental processes, such as germ band closure and neural development [1,7,8,106,107]. Similarities in gene expression and morphology may hint at a common origin of these tissues in onychophorans and arthropods.…”

“…Similar to its spider orthologue, netrin is expressed in the ventral extra-embryonic tissue of the onychophoran E. kanangrensis (figures 6 B , 7 B ; see also fig. 1 in [107]). Possibly, this guidance cue is required for the correct neurogenic wiring in, across and around the ventral midline in panarthropod species with a split ventral germ band.…”

Single-cell RNA sequencing of mid-to-late stage spider embryos: new insights into spider development

“…Cluster-XV) (note that Leite et al [ 111 ] investigated another paralog of this gene, AP2 (LOC107452006)), Fz4.1 (LOC107442148), Fz4.2 (LOC107441380), and unchoordinated-5.1 ( unc5.1 ) (LOC107445619) (e.g. [ 4 , 6 , 45 , 64 , 82 , 83 , 88 , 109 , 111 , 132 , 134 , 141 , 150 , 160 , 167 ].…”

Getting connected: Pathfinding and synaptogenesis in neural development, evolution, and disease

“…The ligands and cell surface receptors guiding axon outgrowth and synapse formation are largely conserved across species emphasizing the functional significance of these pathways. For example, Janssen and Budd show that Netrin and its receptors Unc5 and DCC/Frazzled are expressed in the developing limbs in patterns sufficient to guide innervation conserved between multiple species of arthropods and onychophorans 9 . As described by Cortés and colleagues, 2 differences relate more to the expansion of gene orthologs within individual axon guidance families, an expansion that likely occurred in parallel to the expansion of neural complexity in vertebrates.…”

“…For example, Janssen and Budd show that Netrin and its receptors Unc5 and DCC/Frazzled are expressed in the developing limbs in patterns sufficient to guide innervation conserved between multiple species of arthropods and onychophorans. 9 As described by Cortés and colleagues, 2 differences relate more to the expansion of gene orthologs within individual axon guidance families, an expansion that likely occurred in parallel to the expansion of neural complexity in vertebrates. An interesting exception is the intercellular adhesion molecule DSCAM, which mediates self-avoidance in Drosophila with circuit specificity achieved through extensive alternative splicing.…”