Teneurin trans-axonal signaling prunes topographically missorted axons.

Building precise neural circuits necessitates the elimination of axonal projections that have inaccurately formed during development. Although axonal pruning is a selective process, how it is initiated and controlled in vivo remains unclear. Here, we show that trans-axonal signaling mediated by the cell surface molecules Glypican-3, Teneurin-3, and Latrophilin-3 prunes misrouted retinal axons in the visual system. Retinotopic neuron transplantations revealed that pioneer ventral axons that elongate first along the optic tract instruct the pruning of dorsal axons that missort in that region. Glypican-3 and Teneurin-3 are both selectively expressed by ventral retinal ganglion cells and cooperate for correcting missorted dorsal axons. The adhesion G-protein-coupled receptor Latrophilin-3 signals along dorsal axons to initiate the elimination of topographic sorting errors. Altogether, our findings show an essential function for Glypican-3, Teneurin-3, and Latrophilin-3 in topographic tract organization and demonstrate that axonal pruning can be initiated by signaling among axons themselves.

Nuclear Pore Dysfunction in Neurodegeneration.

The nuclear pore complex (NPC) is a large multimeric structure that is interspersed throughout the membrane of the nucleus and consists of at least 33 protein components. Individual components cooperate within the nuclear pore to facilitate selective passage of materials between the nucleus and cytoplasm while simultaneously performing pore-independent roles throughout the cell. NPC dysfunction is a hallmark of neurodegenerative disorders including Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS). NPC components can become mislocalized or altered in expression in neurodegeneration. These alterations in NPC structure are often detrimental to the neuronal function and ultimately lead to neuronal loss. This review highlights the importance of nucleocytoplasmic transport and NPC integrity and how dysfunction of such may contribute to neurodegeneration.

Live imaging of retinotectal mapping reveals topographic map dynamics and a previously undescribed role for Contactin 2 in map sharpening.

Organization of neuronal connections into topographic maps is essential for processing information. Yet, our understanding of topographic mapping has remained limited by our inability to observe maps forming and refining directly in vivo. Here, we used Cre-mediated recombination of a new colorswitch reporter in zebrafish to generate the first transgenic model allowing the dynamic analysis of retinotectal mapping in vivo. We found that the antero-posterior retinotopic map forms early but remains dynamic, with nasal and temporal retinal axons expanding their projection domains over time. Nasal projections initially arborize in the anterior tectum but progressively refine their projection domain to the posterior tectum, leading to the sharpening of the retinotopic map along the antero-posterior axis. Finally, using a CRISPR-mediated mutagenesis approach, we demonstrate that the refinement of nasal retinal projections requires the adhesion molecule Contactin 2. Altogether, our study provides the first analysis of a topographic map maturing in real time in a live animal and opens new strategies for dissecting the molecular mechanisms underlying precise topographic mapping in vertebrates.

Trans-Axonal Signaling in Neural Circuit Wiring.

The development of neural circuits is a complex process that relies on the proper navigation of axons through their environment to their appropriate targets. While axon-environment and axon-target interactions have long been known as essential for circuit formation, communication between axons themselves has only more recently emerged as another crucial mechanism. Trans-axonal signaling governs many axonal behaviors, including fasciculation for proper guidance to targets, defasciculation for pathfinding at important choice points, repulsion along and within tracts for pre-target sorting and target selection, repulsion at the target for precise synaptic connectivity, and potentially selective degeneration for circuit refinement. This review outlines the recent advances in identifying the molecular mechanisms of trans-axonal signaling and discusses the role of axon-axon interactions during the different steps of neural circuit formation.

Characterization of the caspase family in zebrafish.

First discovered for their role in mediating programmed cell death and inflammatory responses, caspases have now emerged as crucial regulators of other cellular and physiological processes including cell proliferation, differentiation, migration, and survival. In the developing nervous system, for instance, the non-apoptotic functions of caspases have been shown to play critical roles in the formation of neuronal circuits by regulating axon outgrowth, guidance and pruning. How caspase activity is spatially and temporally maintained at sub-lethal levels within cells remains however poorly understood, especially in vivo. Thanks to its transparency and accessibility, the zebrafish offers the unique ability to directly visualize caspase activation in vivo. Yet, detailed information about the caspase family in zebrafish is lacking. Here, we report the identification and characterization of 19 different caspase genes in zebrafish, and show that caspases have diverse expression profiles from cleavage to larval stages, suggesting highly specialized and/or redundant functions during embryonic development.