Caenorhabditis elegans Flamingo FMI-1 controls dendrite self-avoidance through F-actin assembly

Abstract

Self-avoidance is a conserved mechanism that prevents crossover between sister dendrites from the same neuron, ensuring proper functioning of the neuronal circuits. Several adhesion molecules are known to be important for dendrite self-avoidance, but the underlying molecular mechanisms are incompletely defined. Here, we show that FMI-1/Flamingo, an atypical cadherin, is required autonomously for self-avoidance in the multidendritic PVD neuron of Caenorhabditis elegans. The fmi-1 mutant shows increased crossover between sister PVD dendrites. Our genetic analysis suggests that FMI-1 promotes transient F-actin assembly at the tips of contacting sister dendrites to facilitate their efficient retraction during self-avoidance events, probably by interacting with WSP-1/N-WASP. Mutations of vang-1, which encodes the planar cell polarity protein Vangl2 previously shown to inhibit F-actin assembly, suppress self-avoidance defects of the fmi-1 mutant. FMI-1 downregulates VANG-1 levels probably through forming protein complexes. Our study identifies molecular links between Flamingo and the F-actin cytoskeleton that facilitate efficient dendrite self-avoidance.

Neuron tracing and quantitative analyses of dendritic architecture reveal symmetrical three-way-junctions and phenotypes of git-1 in C. elegans

“…This result is in agreement with earlier works that have shown that 3-way junctions represent the minimal energy shape for connecting tubular membrane surfaces [64]. Yet, the observed junction geometry may also be influenced by a local effect of cytoskeletal proteins or membrane coating proteins [65][66][67][68][69][70]. Our findings can therefore serve as a basis for further study of the physical mechanism for stabilization of PVD junctions.…”

Celsr2 Knockout Alleviates Inhibitory Synaptic Stripping and Benefits Motoneuron Survival and Axon Regeneration After Branchial Plexus Avulsion

“…Flamingo is supposed to communicate polarity between neighboring cells and direct the formation of polarized structures via homophilic interactions in many contexts [37]. Molecule-mediated cell-tocell interactions are critical for cellular behaviors involved in many biological processes, such as neuronal migration, self-avoidance of neurite outgrowth, ommatidial formation and epithelial cell organization, and the abnormalities were widely reported in flamingo mutation [38][39][40][41][42]. Celsr2 knockout mice were partially reminiscent of these phenotypes during development, including defective migration of facial motoneurons [26], abnormal cilial organization [27].…”

Dendrite morphogenesis in Caenorhabditis elegans

“…2018 ). Similarly, mutations in the atypical cadherin FMI-1 /Flamingo result in self-avoidance defects, likely through misregulation of the actin cytoskeleton ( Hsu et al . 2020 ).…”