scholarly journals Roles for the adhension molecule Contactin2 in the development and function of neural circuits in zebrafish

2018 ◽  
Author(s):  
◽  
Suman Gurung

Neuronal migration and axon guidance are critical developmental processes that are essential for establishing functional neural circuits underlying complex cognitive and motor functions. Precise neuronal migration and axon guidance are dependent upon cell-cell and cell-substrate interactions, which are mediated by several membrane-associated molecules. The relatively concise segmental organization of the hindbrain and the simple scaffold of axon tracts in the zebrafish brain provides an ideal model to study how different molecules collaborate to guide migrating neurons and growing axons to their final location. In this thesis, I examine the roles of membrane molecules during neuron migration and axon guidance in zebrafish. In Chapter 3, I show the generation of Contactin2 (Cntn2) null mutant using CRISPR/Cas9 and characterize cntn2 mutant. I demonstrate a role for cntn2 in facial branchiomotor (FBM) neuron migration and fasciculation of medial longitudinal fascicle (MLF) axons. In addition, using touch-evoked escape response and swimming assays, I show sensorimotor deficits in cntn2 mutants. Collectively, these data demonstrate distinct developmental roles for zebrafish cntn2 in neuronal migration and axon fasciculation, and in the function of sensorimotor circuits. In Chapter 4, I examine pairwise genetic interactions between several PCP and non-PCP genes for FBM neuron migration. I show that vangl2 is rather unique in exhibiting genetic interactions with several PCP and non-PCP genes. These data suggest that vangl2 might be playing a central role in regulating the function of many PCP and non-PCP genes for FBM neuron migration. In Chapter 6, I describe a novel genetic approach which utilizes the human CD59 receptor (hCD59) and the bacterial toxin intermedilysin (ILY) for rapid cell ablation in zebrafish.


2020 ◽  
Author(s):  
Daniel Z. Doyle ◽  
Mandy M. Lam ◽  
Adel Qalieh ◽  
Yaman Qalieh ◽  
Alice Sorel ◽  
...  

AbstractSubplate neurons indispensably orchestrate the developmental assembly of cortical neural circuits. Here, by cell type-specific dissection of Arid1a function, we uncover an unexpectedly selective role for this ubiquitous chromatin remodeler in subplate neuron molecular identity and circuit wiring function. We find that pan-cortical deletion of Arid1a, but not sparse deletion, leads to mistargeting of callosal and thalamocortical connectivities reminiscent of subplate ablation. These miswiring phenotypes are concomitant with disrupted subplate neuron organization, morphogenesis, axons, and extracellular matrix. Mechanistically, Arid1a is required to establish the transcriptional identity of subplate neurons. Remarkably, cortical plate deletion of Arid1a, which spares subplate neurons, restores subplate axons and extracellular matrix, and is sufficient to extensively correct callosal and thalamocortical axon misrouting, revealing an axon guidance function of Arid1a centered on the subplate. Thus, Arid1a regulates the molecular identity and function of subplate neurons, and thereby non-cell autonomously mediates the formation of cortical connectivity during development.



2018 ◽  
Author(s):  
Inés González-Calvo ◽  
Fekrije Selimi

AbstractMany proteins initially identified in the immune system play roles in neurogenesis, neuronal migration, axon guidance, synaptic plasticity and other processes related to the formation and refinement of neural circuits. Although the function of the immune-related protein Galectin-3 (LGALS3) has been extensively studied in the regulation of inflammation, cancer and microglia activation, little is known about its role in the development of the brain. In this study, we identified that LGALS3 is expressed in the developing postnatal cerebellum. More precisely, LGALS3 is expressed by cells in meninges and in the choroid plexus, and in subpopulations of astrocytes and of microglial cells in the cerebellar cortex. Analysis of Lgals3 knockout mice showed that Lgals3 is dispensable for the development of cerebellar cytoarchitecture and Purkinje cell excitatory synaptogenesis in the mouse.



Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.



2018 ◽  
Vol 103 (6) ◽  
pp. 1009-1021 ◽  
Author(s):  
William B. Dobyns ◽  
Kimberly A. Aldinger ◽  
Gisele E. Ishak ◽  
Ghayda M. Mirzaa ◽  
Andrew E. Timms ◽  
...  


Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4475-4488 ◽  
Author(s):  
Erik A. Lundquist ◽  
Peter W. Reddien ◽  
Erika Hartwieg ◽  
H. Robert Horvitz ◽  
Cornelia I. Bargmann

The Caenorhabditis elegans genome contains three rac-like genes, ced-10, mig-2, and rac-2. We report that ced-10, mig-2 and rac-2 act redundantly in axon pathfinding: inactivating one gene had little effect, but inactivating two or more genes perturbed both axon outgrowth and guidance. mig-2 and ced-10 also have redundant functions in some cell migrations. By contrast, ced-10 is uniquely required for cell-corpse phagocytosis, and mig-2 and rac-2 have only subtle roles in this process. Rac activators are also used differentially. The UNC-73 Trio Rac GTP exchange factor affected all Rac pathways in axon pathfinding and cell migration but did not affect cell-corpse phagocytosis. CED-5 DOCK180, which acts with CED-10 Rac in cell-corpse phagocytosis, acted with MIG-2 but not CED-10 in axon pathfinding. Thus, distinct regulatory proteins modulate Rac activation and function in different developmental processes.



2021 ◽  
Author(s):  
Elie Fink ◽  
Matthieu Louis

Animals differ in their appearances and behaviors. While many genetic studies have addressed the origins of phenotypic differences between fly species, we are still lacking a quantitative assessment of the variability in the way different fly species behave. We tackled this question in one of the most robust behaviors displayed by Drosophila: chemotaxis. At the larval stage, Drosophila melanogaster navigate odor gradients by combining four sensorimotor routines in a multilayered algorithm: a modulation of the overall locomotor speed and turn rate; a bias in turning during down-gradient motion; a bias in turning toward the gradient; the local curl of trajectories toward the gradient ("weathervaning"). Using high-resolution tracking and behavioral quantification, we characterized the olfactory behavior of eight closely related species of the Drosophila group in response to 19 ecologically-relevant odors. Significant changes are observed in the receptive field of each species, which is consistent with the rapid evolution of the peripheral olfactory system. Our results reveal substantial inter-species variability in the algorithms directing larval chemotaxis. While the basic sensorimotor routines are shared, their parametric arrangements can vary dramatically across species. The present analysis sets the stage for deciphering the evolutionary relationships between the structure and function of neural circuits directing orientation behaviors in Drosophila.



Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4545-4552 ◽  
Author(s):  
G. C. Teg Pipes ◽  
Qing Lin ◽  
Stephanie E. Riley ◽  
Corey S. Goodman

A previous genetic screen led to the identification of the beaten path (beat Ia) gene in Drosophila. Beat Ia contains two immunoglobulin (Ig) domains and appears to function as an anti-adhesive factor secreted by specific growth cones to promote axon defasciculation. We identify a family of 14 beat-like genes in Drosophila. In contrast to beat Ia, four novel Beat-family genes encode membrane-bound proteins. Moreover, mutations in each gene lead to much more subtle guidance phenotypes than observed in beat Ia. Genetic interactions between beat Ic and beat Ia reveal complementary functions. Our data suggest a model whereby Beat Ic (and perhaps other membrane-bound family members) functions in a pro-adhesive fashion to regulate fasciculation, while Beat Ia (the original secreted Beat) functions in an anti-adhesive fashion to regulate defasciculation.



EMBO Reports ◽  
2012 ◽  
Vol 13 (4) ◽  
pp. 286-288
Author(s):  
Kristin Scott ◽  
Marc Hammarlund
Keyword(s):  


2020 ◽  
Vol 23 (10) ◽  
pp. 1297-1306 ◽  
Author(s):  
Jiakun Chen ◽  
Kira E. Poskanzer ◽  
Marc R. Freeman ◽  
Kelly R. Monk


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