Structure and evolution of neuronal wiring receptors and ligands

Abstract

One of the fundamental properties of a neuronal circuit is the map of its connections. The cellular and developmental processes that allow for the growth of axons and dendrites, selection of synaptic targets, and formation of functional synapses use neuronal surface receptors and their interactions with other surface receptors, secreted ligands, and matrix molecules. Spatiotemporal regulation of the expression of these receptors and cues allows for specificity in the developmental pathways that wire stereotyped circuits. The families of molecules controlling axon guidance and synapse formation are generally conserved across animals, with some important exceptions, which have consequences for neuronal connectivity. Here, we summarize the distribution of such molecules across multiple taxa, with a focus on model organisms, evolutionary processes that led to the multitude of such molecules, and functional consequences for the diversification or loss of these receptors.

Looking for Guidance – Models and Methods to Study Axonal Navigation

“…Taken together, the guidance of thalamocortical axons uses the same type of mechanisms, chemoattraction and -repulsion, as well as the interaction with intermediate targets that was seen for axon guidance in the spinal cord or in the visual system. In fact, the same molecular pathways were found to be required for the formation of neural circuits in different species (from worms and flies to mice) and throughout the nervous system (Corte´s et al, 2022).…”

Structural insights into the formation of repulsive Netrin guidance complexes

“…Synaptic connectivity of the nervous systems in bilaterian animals is established through a conserved set of wiring molecules, including those that guide the growth of axons and determine synaptic partners (Cortés et al, 2022; Kolodkin and Tessier-Lavigne, 2011; Zang et al, 2021). Netrins are conserved, secreted guidance cues that are unique in their ability to exert attractive and repulsive responses on growing axons (Boyer and Gupton, 2018).…”

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

“…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.…”

“…The sensory systems provide further evidence for the multifaceted functions of large families of traditional axon guidance factors during neuronal circuit assembly. A remarkable aspect of vertebrate neural development is the expansion of genes within families of cell surface proteins and axon guidance factors, and as described by Cortés and colleagues, 2 this has been a hallmark of their evolution. This enables a broad diversification of function as similar guidance cues can be used in distinct combinations to promote alternative outcomes.…”

“…Together, these advances stand alone, and they may also be synthesized toward a better understanding of human disease. Shubham Kale 1 Megan E. Williams 1 Michael R. Deans 1,2…”