Abstract
Spatial arrangement of neurite branching is instructed by both attractive and repulsive cues. Here we show that in C. elegans, the Wnt family of secreted glycoproteins specify neurite branching sites in the PLM mechanosensory neurons. Wnts function through MIG-1/Frizzled and the planar cell polarity protein (PCP) VANG-1/Strabismus/Vangl2 to restrict the formation of F-actin patches, which mark branching sites in nascent neurites. We find that VANG-1 promotes Wnt signaling by facilitating Frizzled endocytosis and genetically acts in a common pathway with arr-1/β-arrestin, whose mutation results in defective PLM branching and F-actin patterns similar to those in the Wnt, mig-1 or vang-1 mutants. On the other hand, the UNC-6/Netrin pathway intersects orthogonally with Wnt-PCP signaling to guide PLM branch growth along the dorsal-ventral axis. Our study provides insights for how attractive and repulsive signals coordinate to sculpt neurite branching patterns, which are critical for circuit connectivity.
Highlights
Branching of the axon or dendrite expands the connectivity of neural circuits and is critical for the functions of the nervous system
We show that the Wnt glycoproteins signal through the Frizzled receptor and the Planar Cell Polarity (PCP) protein VANG-1 to instruct neurite branching in the nematode C. elegans, by restricting filamentous actin (F-actin) assembly to positions along the nascent neurite where future branches emerge
VANG-1 facilitates Frizzled endocytosis and its subsequent signaling in the endosome, which is critical for shaping F-actin assembly
Summary
Branching of the axon or dendrite expands the connectivity of neural circuits and is critical for the functions of the nervous system. Transcription factors have been shown to specify the morphology of neuronal branch arbors as part of cell fate determination [1]. Neurite branching is patterned by inhibitory signals. In the amphibian and vertebrate visual systems, repulsive ephrin-Eph signaling shapes topographic innervation of tectal neurons by preventing ectopic branching of retinal ganglion cells (RGC) beyond the target zones [4,5,6]. Graded Wnt glycoproteins repel the chick RGC axon branches in the tectum [7]. These studies highlight the importance of inhibitory cues in instructing neurite branching patterns
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