scholarly journals A neurite-zippering mechanism, mediated by layer-specific expression of IgCAMs, regulates synaptic laminar specificity in the C. elegans nerve ring neuropil

2020 ◽  
Author(s):  
Titas Sengupta ◽  
Noelle L. Koonce ◽  
Mark W. Moyle ◽  
Leighton H. Duncan ◽  
Nabor Vázquez-Martínez ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Design Principle ◽  
Brain Structures ◽  
Nerve Ring ◽  
Learning Approaches ◽  
Specific Expression ◽  
Synaptic Specificity ◽  
C Elegans ◽  
Regulated Expression ◽  
Laminar Specificity

AbstractA fundamental design principle of nervous systems is the grouping of neuronal contacts into layers within nerve bundles. The layered arrangement of neurites requires nanoscale precision in their placement within bundles, and this precision, which can not be exclusively explained by simple tip-directed outgrowth dynamics, underpins synaptic specificity and circuit architecture. Here we implement novel imaging methods and deep learning approaches to document the specific placement of single neurites during the assembly of the C. elegans nerve ring. We uncover a zippering mechanism that controls precise placement of neurites onto specific layer subdomains. Nanoscale precision in neurite placement is orchestrated via temporally-regulated expression of specific Ig adhesion molecules, such as SYG-1. Ig adhesion molecules act as instructive signals, defining sublaminar regions and guiding neurite zippering onto target neurons. Our study reveals novel developmental mechanisms that coordinate neurite placement and synaptic specificity within layered brain structures.

scholarly journals Differential adhesion regulates neurite placement via a retrograde zippering mechanism

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Titas Sengupta ◽  
Noelle L Koonce ◽  
Nabor Vázquez-Martínez ◽  
Mark W Moyle ◽  
Leighton H Duncan ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Developmentally Regulated ◽  
Synaptic Specificity ◽  
C Elegans ◽  
Differential Adhesion ◽  
Regulated Expression ◽  
Nerve Bundles ◽  
Alternate Mechanism ◽  
Adhesive Forces

During development, neurites and synapses segregate into specific neighborhoods or layers within nerve bundles. The developmental programs guiding placement of neurites in specific layers, and hence their incorporation into specific circuits, are not well understood. We implement novel imaging methods and quantitative models to document the embryonic development of the C. elegans brain neuropil, and discover that differential adhesion mechanisms control precise placement of single neurites onto specific layers. Differential adhesion is orchestrated via developmentally-regulated expression of the IgCAM SYG-1, and its partner ligand SYG-2. Changes in SYG-1 expression across neuropil layers result in changes in adhesive forces, which sort SYG-2-expressing neurons. Sorting to layers occurs, not via outgrowth from the neurite tip, but via an alternate mechanism of retrograde zippering, involving interactions between neurite shafts. Our study indicates that biophysical principles from differential adhesion govern neurite placement and synaptic specificity in vivo in developing neuropil bundles.

scholarly journals Volumetric reconstruction of main Caenorhabditis elegans neuropil at two different time points

2018 ◽  
Author(s):  
Christopher A Brittin ◽  
Steven J Cook ◽  
David H Hall ◽  
Scott W Emmons ◽  
Netta Cohen
Keyword(s):  
Spatial Information ◽  
Genetic Model ◽  
Nerve Ring ◽  
Synaptic Connectivity ◽  
Spatial Proximity ◽  
Detailed Knowledge ◽  
Synaptic Specificity ◽  
Time Points ◽  
C Elegans ◽  
Volumetric Reconstruction

Detailed knowledge of both synaptic connectivity and the spatial proximity of neurons is crucial for understanding wiring specificity in the nervous system. Here, we volumetrically reconstructed the C. Elegans nerve ring from legacy serial-sectioned electron micrographs at two distinct time points: the L4 and young adult. The new volumetric reconstructions provide detailed spatial and morphological information of neural processes in the nerve ring. Our analysis suggests that the nerve ring exhibits three levels of wiring specificity: spatial, synaptic and subcellular. Neuron classes innervate well defined neighborhoods and aggregate functionally similar synapses to support distinct computational pathways. Connectivity fractions vary based on neuron class and synapse type. We find that the variability in process placement accounts for less than 20% of the variability in synaptic connectivity and models based only on spatial information cannot account for the reproducibility of synaptic connections among homologous neurons. This suggests that additional, non-spatial factors also contribute to synaptic and subcellular specificity. With this in mind, we conjecture that a spatially constrained, genetic model could provide sufficient synaptic specificity. Using a model of cell-specific combinatorial genetic expression, we show that additional specificity, such as sub-cellular domains or alternative splicing, would be required to reproduce the wiring specificity in the nerve ring.

scholarly journals Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons

2016 ◽  
Vol 113 (35) ◽  
pp. E5222-E5231 ◽  
Author(s):  
Csaba Földy ◽  
Spyros Darmanis ◽  
Jason Aoto ◽  
Robert C. Malenka ◽  
Stephen R. Quake ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Cell ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Expression Profiles ◽  
Projection Neurons ◽  
Specific Expression ◽  
Synaptic Specificity ◽  
Genes Encoding ◽  
Cell Type Specific Expression

In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.

scholarly journals pop-1/TCF, ref-2/ZIC and T-box factors regulate the development of anterior cells in the C. elegans embryo

2021 ◽  
Author(s):  
Jonathan D Rumley ◽  
Elicia A Preston ◽  
Dylan Cook ◽  
Felicia L Peng ◽  
Amanda L Zacharias ◽  
...  
Keyword(s):  
Wnt Pathway ◽  
Expression Patterns ◽  
Specific Expression ◽  
T Box ◽  
Animal Development ◽  
C Elegans ◽  
The Many ◽  
Necessary And Sufficient ◽  
Cell Division Timing ◽  
Anterior Posterior

Patterning of the anterior-posterior axis is fundamental to animal development. The Wnt pathway plays a major role in this process by activating the expression of posterior genes in animals from worms to humans. This observation raises the question of whether the Wnt pathway or other regulators control the expression of the many anterior-expressed genes. We found that the expression of five anterior-specific genes in Caenorhabditis elegans embryos depends on the Wnt pathway effectors pop-1/TCF and sys-1/β-catenin. We focused further on one of these anterior genes, ref-2/ZIC, a conserved transcription factor expressed in multiple anterior lineages. Live imaging of ref-2 mutant embryos identified defects in cell division timing and position in anterior lineages. Cis-regulatory dissection identified three ref-2 transcriptional enhancers, one of which is necessary and sufficient for anterior-specific expression. This enhancer is activated by the T-box transcription factors TBX-37 and TBX-38, and surprisingly, concatemerized TBX-37/38 binding sites are sufficient to drive anterior-biased expression alone, despite the broad expression of TBX-37 and TBX-38. Taken together, our results highlight the diverse mechanisms used to regulate anterior expression patterns in the embryo.

scholarly journals Multicellular rosettes organize neuropil formation

2020 ◽  
Author(s):  
Christopher A. Brittin ◽  
Anthony Santella ◽  
Kristopher Barnes ◽  
Mark W. Moyle ◽  
Li Fan ◽  
...  
Keyword(s):  
Functional Organization ◽  
Critical Role ◽  
Ring Structure ◽  
Nerve Ring ◽  
Cell Behaviors ◽  
Dense Networks ◽  
C Elegans ◽  
Single Axon ◽  
Organizational Features

SummaryNeuropils are compartments in the nervous system containing dense networks of neurites and synapses which function as information processing centers. Neuropil formation requires structural and functional organization at and across different scales, achieving single-axon precision for circuits that carry out the core functions while simultaneously accommodating variability among individuals [1; 2; 3; 4]. How these organizational features emerge over development is poorly understood. The nerve ring is the primary neuropil in C. elegans, and its structure is thoroughly mapped [5; 6]. We show that prior to axon outgrowth, nerve ring neurons form a ring of multicellular rosettes with surrounding cells to organize the stratified nerve ring structure [7; 8]. Axon bundles which correspond to future nerve ring strata grow from rosette centers, travel along the ring on “bridge” cells that are simultaneously engaged in adjacent rosettes, and assemble into a topographic scaffold of the nerve ring. SAX-3/Robo is required for proper rosette formation and outgrowth from the center. Furthermore, axon contact sites that form early in development are more conserved than the later ones, indicating a temporal component in neuropil structural variability. Our results reveal an unexpected and critical role of collective cell behaviors prior to innervation to pattern a complex neuropil and orchestrate its formation across scales.

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