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Moyle et al. 2021

Structural and developmental principles of neuropil assembly in C. elegans

Mark W. Moyle, Kristopher M. Barnes, Manik Kuchroo, Alex Gonopolskiy, Leighton H. Duncan, Titas Sengupta, Lin Shao, Min Guo, Anthony Santella, Ryan Christensen, Abhishek Kumar, Yicong Wu, Kevin R. Moon, Guy Wolf, Smita Krishnaswamy, Zhirong Bao, Hari Shroff, William A. Mohler and Daniel A. Colón-Ramos
Nature volume 591, pages 99–104
Published: 24 February 2021

Summary

  • The C. elegans nerve ring neuropil is organized into four distinct layers (strata), each corresponding to specific behavioural circuits. These strata reflect a topographic and functional segregation of sensory inputs and motor outputs along the anterior–posterior axis of the worm.

  • The authors developed and applied a novel “diffusion condensation” clustering algorithm with 3D visualization (C-PHATE) to analyze over 100,000 neuron-neuron contact instances. This revealed nested structural and circuit relationships that differ from traditional synaptic connectivity maps.

  • A subset of highly connected interneurons, termed “rich-club” neurons, bridge across multiple strata and function as key integrators of neural circuits, supporting communication between segregated layers and facilitating complex behaviors.

  • Using in vivo 4D imaging and cell tracking, the study showed that neuropil assembly is guided by early outgrowth from a small group of centrally located “pioneer” neurons in stratum S2. This initiates an inside-out developmental sequence essential for forming the layered architecture.