scholarly journals Pax6 is required for the normal development of the forebrain axonal connections

Development ◽  
2002 ◽  
Vol 129 (21) ◽  
pp. 5041-5052 ◽  
Author(s):  
Lucy Jones ◽  
Guillermina López-Bendito ◽  
Peter Gruss ◽  
Anastassia Stoykova ◽  
Zoltán Molnár
Keyword(s):  
Knockout Mouse ◽  
Normal Development ◽  
Internal Capsule ◽  
Axonal Guidance ◽  
Pax6 Expression ◽  
Dye Tracing ◽  
Axonal Connections ◽  
Carbocyanine Dye ◽  
Ventral Thalamus ◽  
Guidance Molecule

The transcription factor PAX6 has been implicated in forebrain patterning,cerebral cortical arealization and in development of thalamocortical connections. Using a Pax6/lacZ knockout mouse, in which the endogenous Pax6 expression is reflected by β-galactosidase activity, we have studied the consequences of the loss of Pax6function on thalamocortical (TCA) and corticofugal axon (CFA) pathfinding during the period of embryonic day (E) 14.5 to E18.5. Carbocyanine dye tracing in Pax6 heterozygotes (Pax6+/-) and Pax6wild-type (Pax6+/+) brains revealed that CFAs and TCAs temporarily arrested their growth at E14.5 at the border of theβ-galactosidase-positive region at the pallial/subpallial boundary(PSPB), before they continued towards their targets. However, in Pax6homozygous (Pax6-/-) embryos, CFAs and TCAs were unable to encounter each other at the PSPB and reach their final targets. Instead of crossing the PSPB, they had the tendency to descend into the ventral pallium in large aberrant fascicles. In addition, cells with a presumptive guide-post function, which are normally situated in the ventral thalamus, internal capsule and hypothalamus, were more dispersed in the hypothalamus and ventral pallium. These pathfinding defects were confirmed by immunohistochemistry for L1 and TAG1, markers of the early axonal connections. The aberrant development of axonal connections in absence of Pax6 function appear to be related to ultrastructural defects of cells along the PSPB, as well as to a failure of axonal guidance molecule expression, including Sema3c and Sema5a.

scholarly journals Vagus nerve controls resolution and pro-resolving mediators of inflammation

2014 ◽  
Vol 211 (6) ◽  
pp. 1037-1048 ◽  
Author(s):  
Valbona Mirakaj ◽  
Jesmond Dalli ◽  
Tiago Granja ◽  
Peter Rosenberger ◽  
Charles N. Serhan
Keyword(s):  
Vagus Nerve ◽  
Lipid Mediators ◽  
Axonal Guidance ◽  
Resolvin D1 ◽  
Neutrophil Influx ◽  
Proinflammatory Mediators ◽  
Neuronal Control ◽  
Mediators Of Inflammation ◽  
Guidance Molecule ◽  
Local Expression

Resolution of inflammation is now recognized as a biosynthetically active process involving pro-resolving mediators. Here, we show in zymosan-initiated peritoneal inflammation that the vagus nerve regulates local expression of netrin-1, an axonal guidance molecule that activates resolution, and that vagotomy reduced local pro-resolving mediators, thereby delaying resolution. In netrin-1+/− mice, resolvin D1 (RvD1) was less effective in reducing neutrophil influx promoting resolution of peritonitis compared with Ntn1+/+. Netrin-1 shortened the resolution interval, decreasing exudate neutrophils, reducing proinflammatory mediators, and stimulating the production of resolvins, protectins, and lipoxins. Human monocytes incubated with netrin-1 produced proresolving mediators, including resolvins and lipoxins. Netrin-1 and RvD1 displayed bidirectional activation in that they stimulated each other’s expression and enhanced efferocytosis. These results indicate that the vagus nerve regulates both netrin-1 and pro-resolving lipid mediators, which act in a bidirectional fashion to stimulate resolution, and provide evidence for a novel mechanism for local neuronal control of resolution.

In vitro experiments on axonal guidance and growth-cone collapse

1990 ◽  
Vol 153 (1) ◽  
pp. 29-46
Author(s):  
B. Muller ◽  
B. Stahl ◽  
F. Bonhoeffer
Keyword(s):  
Anterior Part ◽  
Lipid Vesicles ◽  
Axonal Guidance ◽  
In Vitro Experiments ◽  
Growth Cone Collapse ◽  
Retinal Axons ◽  
Regional Specificity ◽  
Membrane Components ◽  
Guidance Molecule

In the retinotectal projection, nasal retinal axons project to posterior tectum, while temporal axons project to the anterior part of the tectum. In in vitro experiments, a similar specificity can be observed: the nasal and temporal retinal axons can be guided by tectal membrane components so that, for example, temporal retinal axons, when growing on a striped substratum consisting of anterior and posterior tectal membranes, express a very strong preference for the anterior stripes. This preference is not due to attractivity of anterior membranes but rather to avoidance of posterior material, although the pure posterior membranes are a very good substratum for growth of temporal axons. The repellent guidance molecule has been identified. Interestingly, besides guidance this molecule causes another reaction: when growing temporal axons are exposed to medium containing either posterior membranes or artificial lipid vesicles containing the repellent guidance molecule, the axonal growth cones collapse. As in guidance, there is a clear regional specificity: e.g. the repellent guidance molecule derived from posterior tectum induces collapse of temporal but not of nasal axons. Since the guiding and the collapse-inducing activity are expressed by one and the same glycoprotein molecule (Mr 33 × 10(3), linked to the membrane by phosphatidylinositol) and since another molecule has been identified by Keynes' group which also expresses both guiding and collapse-inducing activity, one might speculate that axonal guidance and axonal collapse have something in common. Models of axonal guidance will be discussed.

Segmental and neuronal architecture of the hindbrain of Krox-20 mouse mutants

Development ◽  
1997 ◽  
Vol 124 (6) ◽  
pp. 1215-1226 ◽  
Author(s):  
S. Schneider-Maunoury ◽  
T. Seitanidou ◽  
P. Charnay ◽  
A. Lumsden
Keyword(s):  
Branchial Arch ◽  
Motor Nucleus ◽  
Exit Point ◽  
Dye Tracing ◽  
Trigeminal Motor Nucleus ◽  
Zinc Finger Transcription Factor ◽  
Mouse Mutants ◽  
Neuron Populations ◽  
Carbocyanine Dye ◽  
Internal Architecture

The vertebrate hindbrain is transiently segmented during its early development with the formation of reiterated bulges, the rhombomeres (r). The Krox-20 gene, which encodes a zinc finger transcription factor, has been shown previously to be implicated in the maintenance of r3 and r5 (Schneider-Maunoury, S., Topilko, P., Seitanidou, T., Levi, G., Cohen-Tannoudji, M., Pournin, S., Babinet, C. and Charnay, P. (1993) Cell 75, 1199–1214; Swiatek, P. J. and Gridley, T. (1993) Genes Dev. 7, 2071–2084. However, it was not clear from these analyses how extensive the deletion of r3 and r5 was and whether the overall segmentation and internal architecture of the hindbrain was affected. We have now reinvestigated these issues by analysis of rhombomere boundaries, using both morphological and molecular markers, and of the fate of specific motor neuron populations, using retrograde and anterograde carbocyanine dye tracing. We conclude that r3 and r5 and their derivatives are completely eliminated in Krox-20(−/−) embryos while overall hindbrain segmentation is maintained. In addition, we show that the disappearance of these territories has important consequences for even-numbered rhombomeres as well, in particular on axonal navigation: (i) a population of r6 motoneurons, presumably normally fated to join the glossopharyngeal nerve, has its axons misrouted toward the facial exit point in r4; (ii) the trigeminal motor axons are also misrouted, presumably because of the proximity of the trigeminal and facial exit points. They fasciculate with facial axons outside the neural tube and enter the second branchial arch instead of the first arch. This navigational error could explain the disappearance, at around 17.5 dpc, of the trigeminal motor nucleus in Krox-20(−/−) embryos by inadequate supply of essential, possibly arch-specific survival factors.

scholarly journals Chromophore-assisted laser inactivation of a repulsive axonal guidance molecule

1996 ◽  
Vol 6 (11) ◽  
pp. 1497-1502 ◽  
Author(s):  
B.K. Müller ◽  
D.G. Jay ◽  
F. Bonhoeffer
Keyword(s):  
Axonal Guidance ◽  
Guidance Molecule

scholarly journals Growth cone repulsion to Netrin-1 depends on lipid raft microdomains enriched in UNC5 receptors

2020 ◽  
Author(s):  
Marc Hernaiz-Llorens ◽  
Cristina Roselló-Busquets ◽  
Nela Durisic ◽  
Adam Filip ◽  
Fausto Ulloa ◽  
...  
Keyword(s):  
Single Particle Tracking ◽  
Axonal Guidance ◽  
Neuronal Cultures ◽  
Membrane Raft ◽  
Primary Neuronal Cultures ◽  
Specific Localization ◽  
Functional Consequences ◽  
Axonal Extension ◽  
Lipid Raft Microdomains ◽  
Guidance Molecule

Abstract During brain development, Uncoordinated locomotion 5 (UNC5) receptors control axonal extension through their sensing of the guidance molecule Netrin-1. The correct positioning of receptors into cholesterol-enriched membrane raft microdomains is crucial for the efficient transduction of the recognized signals. However, whether such microdomains are required for the appropriate axonal guidance mediated by UNC5 receptors remains unknown. Here, we combine the use of confocal microscopy, live-cell FRAP analysis and single-particle tracking PALM to characterize the distribution of UNC5 receptors into raft microdomains, revealing differences in their membrane mobility properties. Using pharmacological and genetic approaches in primary neuronal cultures and brain cerebellar explants we further demonstrate that disrupting raft microdomains inhibits the chemorepulsive response of growth cones and axons against Netrin-1. Together, our findings indicate that the distribution of all UNC5 receptors into cholesterol-enriched raft microdomains is heterogeneous and that the specific localization has functional consequences for the axonal chemorepulsion against Netrin-1.

scholarly journals OTOGL, a gelforming mucin protein, is nonessential for male germ cell development and spermatogenesis in mice

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiming Li ◽  
Yan Zhang ◽  
Xinzong Zhang ◽  
Congcong Cao ◽  
Xiaomin Luo ◽  
...  
Keyword(s):  
Germ Cell ◽  
Knockout Mouse ◽  
Histological Analysis ◽  
Normal Development ◽  
Biological Function ◽  
Cell Development ◽  
Male Germ Cell ◽  
Seminiferous Tubules ◽  
Obstructive Azoospermia ◽  
Germ Cell Development

AbstractOtogelin-like protein (encoded by Otogl) was highly structural similar to the gelforming mucin proteins. Although human OTOG mutations have been linked to deafness, the biological function of OTOGL in male germ cell development remains enigmatic. In screening 336 patients with non-obstructive azoospermia (NOA), OTOGL displays the high mutant ratio (13.99 %). Then, we examined the expression of OTOGL in developing mouse testes. Otogl mRNA and protein are continually expressed in postnatal developing testes from postnatal day 0 (P0) testes to P21 testes exhibiting a decreased trend with the age growth. We thus generated a global Otogl knockout mouse (KO) model using the CRISPR/Cas9 technology; however, Otogl KO mice displayed normal development and fertility. Further histological analysis of Otogl knockout mouse testes revealed that all types of spermatogenic cells are present in Otogl KO seminiferous tubules. Together, our study suggested that OTOGL is nonessential for male germ cell development and spermatogenesis.

Modulation of Giα2 signaling by the axonal guidance molecule UNC5H2

2002 ◽  
Vol 297 (4) ◽  
pp. 898-905 ◽  
Author(s):  
Katsumi Komatsuzaki ◽  
Sussie Dalvin ◽  
T Bernard Kinane
Keyword(s):  
Axonal Guidance ◽  
Guidance Molecule

scholarly journals Semaphorin-Plexin signaling influences early ventral telencephalic development and thalamocortical axon guidance

2017 ◽  
Author(s):  
Manuela D. Mitsogiannis ◽  
Graham E. Little ◽  
Kevin J. Mitchell
Keyword(s):  
Axon Guidance ◽  
Internal Capsule ◽  
Dorsal Lateral Geniculate Nucleus ◽  
Cell Populations ◽  
Axonal Connections ◽  
Spatiotemporal Expression ◽  
Thalamocortical Axons ◽  
Null Mutant Mice ◽  
Dorsal Lateral Geniculate ◽  
Intermediate Targets

AbstractBackgroundSensory processing relies on projections from the thalamus to the neocortex being established during development. Information from different sensory modalities reaching the thalamus is segregated into specialized nuclei, whose neurons then send inputs to cognate cortical areas through topographically defined axonal connections.Developing thalamocortical axons (TCAs) normally approach the cortex by extending through the subpallium; here, axonal navigation is aided by distributed guidance cues and discrete cell populations, such as the corridor neurons and the internal capsule (IC) guidepost cells. In mice lacking Semaphorin-6A, axons from the dorsal lateral geniculate nucleus (dLGN) bypass the IC and extend aberrantly in the ventral subpallium. The functions normally mediated by Semaphorin-6A in this system remain unknown, but might depend on interactions with Plexin-A2 and Plexin-A4, which have been implicated in other neurodevelopmental processes.MethodsWe performed immunohistochemical and neuroanatomical analyses of thalamocortical wiring and subpallial development in Sema6a and Plxna2;Plxna4 null mutant mice and analyzed the expression of these genes in relevant structures.ResultsIn Plxna2;Plxna4 double mutants we discovered TCA pathfinding defects that mirrored those observed in Sema6a mutants, suggesting that Semaphorin-6A–Plexin-A2/Plexin-A4 signaling might mediate dLGN axon guidance at subpallial level.In order to understand where and when Semaphorin-6A, Plexin-A2 and Plexin-A4 may be required for proper subpallial TCA guidance, we then characterized their spatiotemporal expression dynamics during early TCA development. We observed that the thalamic neurons whose axons are misrouted in these mutants normally express Semaphorin-6A but not Plexin-A2 or Plexin-A4. By contrast, all three proteins are expressed in corridor cells and other structures in the developing basal ganglia.This could be consistent with the Plexins acting as guidance signals through Sema6A as a receptor on dLGN axons, and/or with an indirect effect on TCA guidance due to functions in morphogenesis of subpallial intermediate targets. In support of the latter possibility, we observed that in both Plxna2;Plxna4 and Sema6a mutants some IC guidepost cells abnormally localize in correspondence of the ventral path misrouted TCAs elongate into.ConclusionsThese findings implicate Semaphorin-6A–Plexin-A2/Plexin-A4 interactions in dLGN axon guidance and in the spatiotemporal organization of guidepost cell populations in the mammalian subpallium.

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