Cadherins in Brain Morphogenesis and Wiring

2012 ◽  
Vol 92 (2) ◽  
pp. 597-634 ◽  
Author(s):  
Shinji Hirano ◽  
Masatoshi Takeichi
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Cell Polarity ◽  
Neural Development ◽  
Planar Cell Polarity ◽  
The Past ◽  
Vertebrate Brain ◽  
Dependent Cell ◽  
And Function ◽  
Neural Disorders

Cadherins are Ca2+-dependent cell-cell adhesion molecules that play critical roles in animal morphogenesis. Various cadherin-related molecules have also been identified, which show diverse functions, not only for the regulation of cell adhesion but also for that of cell proliferation and planar cell polarity. During the past decade, understanding of the roles of these molecules in the nervous system has significantly progressed. They are important not only for the development of the nervous system but also for its functions and, in turn, for neural disorders. In this review, we discuss the roles of cadherins and related molecules in neural development and function in the vertebrate brain.

scholarly journals Heparan sulfate molecules mediate synapse formation and function of male mating neural circuits in C. elegans

2018 ◽  
Author(s):  
María I. Lázaro-Peña ◽  
Carlos A. Díaz-Balzac ◽  
Hannes E. Bülow ◽  
Scott W. Emmons
Keyword(s):  
Nervous System ◽  
Cell Adhesion ◽  
Neural Cell ◽  
Male Mating ◽  
Synaptic Connections ◽  
Adhesion Protein ◽  
C Elegans ◽  
Neural Cell Adhesion ◽  
Heparan Sulfates ◽  
And Function

AbstractThe nervous system regulates complex behaviors through a network of neurons interconnected by synapses. How specific synaptic connections are genetically determined is still unclear. Male mating is the most complex behavior in C. elegans. It is composed of sequential steps that are governed by more than 3,000 chemical connections. Here we show that heparan sulfates (HS) play a role in the formation and function of the male neural network. Cell-autonomous and non-autonomous 3-O sulfation by the HS modification enzyme HST-3.1/HS 3-O-sulfotransferase, localized to the HSPG glypicans LON-2/glypican and GPN-1/glypican, was specifically required for response to hermaphrodite contact during mating. Loss of 3-O sulfation resulted in the presynaptic accumulation of RAB-3, a molecule that localizes to synaptic vesicles, disrupting the formation of synapses in a component of the mating circuits. We also show that neural cell adhesion protein neurexin promotes and neural cell adhesion protein neuroligin inhibits formation of the same set of synapses in a parallel pathway. Thus, neural cell adhesion proteins and extracellular matrix components act together in the formation of synaptic connections.Author SummaryThe formation of the nervous system requires the function of several genetically-encoded proteins to form complex networks. Enzymatically-generated modifications of these proteins play a crucial role during this process. These authors analyzed the role of heparan sulfates in the process of synaptogenesis in the male tail of C. elegans. A modification of heparan sulfate is required for the formation of specific synapses between neurons by acting cell-autonomously and non-autonomously. Could it be that heparan sulfates and their diverse modifications are a component of the specification factor that neurons use to make such large numbers of connections unique?

scholarly journals MicroRNAs Regulate Multiple Aspects of Locomotor Behavior in Drosophila

2019 ◽  
Vol 10 (1) ◽  
pp. 43-55
Author(s):  
Nathan C. Donelson ◽  
Richa Dixit ◽  
Israel Pichardo-Casas ◽  
Eva Y. Chiu ◽  
Robert T. Ohman ◽  
...  
Keyword(s):  
Nervous System ◽  
Neural Development ◽  
Locomotor Behavior ◽  
Temperature Dependent ◽  
Motor Circuits ◽  
The Many ◽  
And Function ◽  
Post Transcriptional Regulation ◽  
Movement Tracking

Locomotion is an ancient and fundamental output of the nervous system required for animals to perform many other complex behaviors. Although the formation of motor circuits is known to be under developmental control of transcriptional mechanisms that define the fates and connectivity of the many neurons, glia and muscle constituents of these circuits, relatively little is known about the role of post-transcriptional regulation of locomotor behavior. MicroRNAs have emerged as a potentially rich source of modulators for neural development and function. In order to define the microRNAs required for normal locomotion in Drosophila melanogaster, we utilized a set of transgenic Gal4-dependent competitive inhibitors (microRNA sponges, or miR-SPs) to functionally assess ca. 140 high-confidence Drosophila microRNAs using automated quantitative movement tracking systems followed by multiparametric analysis. Using ubiquitous expression of miR-SP constructs, we identified a large number of microRNAs that modulate aspects of normal baseline adult locomotion. Addition of temperature-dependent Gal80 to identify microRNAs that act during adulthood revealed that the majority of these microRNAs play developmental roles. Comparison of ubiquitous and neural-specific miR-SP expression suggests that most of these microRNAs function within the nervous system. Parallel analyses of spontaneous locomotion in adults and in larvae also reveal that very few of the microRNAs required in the adult overlap with those that control the behavior of larval motor circuits. These screens suggest that a rich regulatory landscape underlies the formation and function of motor circuits and that many of these mechanisms are stage and/or parameter-specific.

scholarly journals Childhood Adversity and Neural Development: A Systematic Review

2019 ◽  
Vol 1 (1) ◽  
pp. 277-312 ◽  
Author(s):  
Katie A. McLaughlin ◽  
David Weissman ◽  
Debbie Bitrán
Keyword(s):  
Systematic Review ◽  
Neural Development ◽  
Childhood Adversity ◽  
Hippocampal Volume ◽  
Extensive Literature ◽  
Dimensional Model ◽  
Neural Structure ◽  
The Past ◽  
Acceleration Model ◽  
And Function

An extensive literature on childhood adversity and neurodevelopment has emerged over the past decade. We evaluate two conceptual models of adversity and neurodevelopment—the dimensional model of adversity and stress acceleration model—in a systematic review of 109 studies using MRI-based measures of neural structure and function in children and adolescents. Consistent with the dimensional model, children exposed to threat had reduced amygdala, medial prefrontal cortex (mPFC), and hippocampal volume and heightened amygdala activation to threat in a majority of studies; these patterns were not observed consistently in children exposed to deprivation. In contrast, reduced volume and altered function in frontoparietal regions were observed consistently in children exposed to deprivation but not children exposed to threat. Evidence for accelerated development in amygdala-mPFC circuits was limited but emerged in other metrics of neurodevelopment. Progress in charting neurodevelopmental consequences of adversity requires larger samples, longitudinal designs, and more precise assessments of adversity.

scholarly journals Ancestral roles of atypical cadherins in planar cell polarity

2020 ◽  
Vol 117 (32) ◽  
pp. 19310-19320
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Sister Group ◽  
The Body ◽  
Cell Alignment ◽  
Actin Organization ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Local Cell

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

scholarly journals Ancestral role of Fat-like cadherins in planar cell polarity

2019 ◽  
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Radial Symmetry ◽  
Global Alignment ◽  
Cell Alignment ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Simple Body ◽  
Epithelial Layers

ABSTRACTFat family cadherins are enormous proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterian animals. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in Hydra, a member of the early-diverging metazoan phylum Cnidaria. Hydra has a simple body plan with only two epithelial layers and radial symmetry. We find that Hydra homologues of Fat-like (HyFat) and Dachsous (HyDs) co-localize at the apico-lateral membrane of ectodermal epithelial cells. Remarkably, HyFat is planar polarized perpendicular to the oral-aboral axis of the animal. Using knockdown approaches we found that HyFat is involved in the regulation of local cell alignment, but is dispensable for the global alignment of ectodermal myonemes along the oral-aboral axis. The intracellular domain (ICD) of HyFat is involved in the morphogenesis of ectodermal myonemes. Thus, Fat family cadherins have ancient, prebilaterian functions in cell adhesion, tissue organization and planar polarity.

scholarly journals Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity

2019 ◽  
Author(s):  
Lydie Flasse ◽  
Siham Yennek ◽  
Cédric Cortijo ◽  
Irene Seijo Barandiaran ◽  
Marine R-C Kraus ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Transmembrane Protein ◽  
Pancreatic Ducts ◽  
Apical Surface ◽  
Epithelial Integrity ◽  
Ductal Cells ◽  
And Function ◽  
Rock Activity

ABSTRACTCell polarity is essential for the architecture and function of numerous epithelial tissues. Here we show how planar cell polarity (PCP), so far studied principally in flat epithelia, is deployed during the morphogenesis of a tubular organ. Using the mammalian pancreas as a model, we report that components of the core PCP pathway such as the transmembrane protein Van Gogh-like (VANGL), are progressively apically-restricted. VANGL expression becomes asymmetrically localized at the apical surface of ductal cells, revealing a planar polarization of the pancreatic duct. We further show that restricting VANGL to these discrete sites of expression is crucial for epithelial integrity. Expansion of expression on basolateral membranes of the progenitors leads to their death and extrusion from the epithelium, as previously observed for perturbations of apico-basal polarity. Using organoids and in vivo analyses, we show that cell elimination is induced by a decrease of Rock activity via Dishevelled.

scholarly journals Planar cell polarity signalling regulates cell adhesion properties in progenitors of the zebrafish laterality organ

Development ◽  
2010 ◽  
Vol 137 (20) ◽  
pp. 3459-3468 ◽  
Author(s):  
P. Oteiza ◽  
M. Koppen ◽  
M. Krieg ◽  
E. Pulgar ◽  
C. Farias ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Adhesion Properties ◽  
Planar Cell Polarity Signalling

Shaping the nervous system: role of the core planar cell polarity genes

2013 ◽  
Vol 14 (8) ◽  
pp. 525-535 ◽  
Author(s):  
Fadel Tissir ◽  
André M. Goffinet
Keyword(s):  
Nervous System ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
The Core
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