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 The tight junctions protein Claudin-5 limits endothelial cell motility

2020 ◽  
pp. jcs.248237
Author(s):  
Zhenguo Yang ◽  
Shuilong Wu ◽  
Federica Fontana ◽  
Yanyu Li ◽  
Wei Xiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Motility ◽  
Dorsal Aorta ◽  
Aortic Endothelial Cells ◽  
Differential Adhesion ◽  
Adhesive Forces

Steinberg's differential adhesion hypothesis suggests that adhesive mechanisms are important for sorting of cells and tissues during morphogenesis (Steinberg, 2007). During zebrafish vasculogenesis, endothelial cells sort into arterial and venous vessel beds but it is unknown whether this involves adhesive mechanisms. Claudins are tight junction proteins regulating the permeability of epithelial and endothelial tissue barriers. Previously, the roles of Claudins during organ development have exclusively been related to their canonical functions in determining paracellular permeability. Here, we use atomic force microscopy to quantify Claudin-5-dependent adhesion and find that this strongly contributes to the adhesive forces between arterial endothelial cells. Based on genetic manipulations, we reveal a non-canonical role of Claudin-5a during zebrafish vasculogenesis, which involves the regulation of adhesive forces between adjacent dorsal aortic endothelial cells. In vitro and in vivo studies demonstrate that loss of Claudin-5 results in increased motility of dorsal aorta endothelial cells and in a failure of the dorsal aorta to lumenize. Our findings uncover a novel role of Claudin-5 in limiting arterial endothelial cell motility, which goes beyond its traditional sealing function during embryonic development.

Early C. elegans embryos are transcriptionally active

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1303-1317 ◽  
Author(s):  
I.E. Schauer ◽  
W.B. Wood
Keyword(s):  
Rna Synthesis ◽  
Developmentally Regulated ◽  
C Elegans ◽  
Nucleotide Incorporation ◽  
Expected Size Range ◽  
Small Set ◽  
Early Transcription ◽  
Incorporation Assay

We have developed a nucleotide incorporation assay for run-on transcription in C. elegans embryonic extracts as an approach to characterizing early transcription. The incorporation is primarily polymerase II-catalyzed RNA synthesis, producing transcripts of the expected size range for mRNAs. Incorporation is insensitive to inhibitors of reinitiation, indicating that the activity represents primarily elongation of nascent chains initiated prior to extract preparation. The transcripts produced appear to be unprocessed pre-mRNAs. Hybridization of labeled transcripts from extracts of staged embryos to a set of cloned genes suggests that the specificity of the in vitro reaction accurately reflects developmentally regulated in vivo transcription. Comparative analyses of transcription in extracts from various stages indicate that pregastrulation embryos are active transcriptionally and that the level of transcription per nucleus is approximately constant throughout embryogenesis. Furthermore, most embryonically expressed genes are already being transcribed in pregastrulation embryos. We also demonstrate that the labeled embryonic run-on transcripts can be used as probes to screen for sequences transcribed preferentially in pregastrulation embryos. There appears to be only a small set of such sequences, which could represent a previously unsuspected class of embryonically transcribed genes important for early embryogenesis.

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.

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