Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system

Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 671-680 ◽  
Author(s):  
Takahiko Kawasaki ◽  
Yoko Bekku ◽  
Fumikazu Suto ◽  
Takashi Kitsukawa ◽  
Masahiko Taniguchi ◽  
...  
Keyword(s):  
Mutant Mouse ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Wild Type ◽  
Migration Activity ◽  
Targeted Gene Disruption ◽  
Neuropilin 1 ◽  
Target Sites ◽  
Mutant Mouse Embryos

Neuropilin 1 is the specific receptor for Sema3A and plays a role in nerve fiber guidance. We report that neuropilin 1 and Sema3A mutant mouse embryos, generated by targeted gene disruption, showed displacement of sympathetic neurons and their precursors and abnormal morphogenesis in the sympathetic trunk. We also show that Sema3A suppressed the cell migration activity of sympathetic neurons from wild-type but not neuropilin 1 mutant embryos in vitro and instead promoted their accumulation into compact cell masses and fasciculation of their neurites. These findings suggest that the neuropilin 1-mediated Sema3A signals regulate arrest and aggregation of sympathetic neuron precursors and sympathetic neurons themselves at defined target sites and axon fasciculation to produce the stereotyped sympathetic nerve pattern.

VSM growth is stimulated in sympathetic neuron/VSM cocultures: role of TGF-β2 and endothelin

2000 ◽  
Vol 278 (2) ◽  
pp. H404-H411 ◽  
Author(s):  
Deborah H. Damon
Keyword(s):  
Transforming Growth Factor ◽  
Sympathetic Neurons ◽  
Sympathetic Nerves ◽  
Sympathetic Neuron ◽  
Vessel Growth ◽  
Coculture Model ◽  
Transforming Growth Factor Β2 ◽  
Cervical Ganglia ◽  
Stimulation Of

Sympathetic nerves are purported to stimulate blood vessel growth. The mechanism(s) underlying this stimulation has not been determined. With use of an in vitro coculture model, the present study tests the hypothesis that sympathetic neurons stimulate the growth of vascular smooth muscle (VSM) and evaluates potential mechanisms mediating this stimulation. Sympathetic neurons isolated from superior cervical ganglia (SCG) stimulated the growth of VSM. Growth of VSM in the presence of SCG (856 ± 81%) was significantly greater than that in the absence of SCG (626 ± 66%, P < 0.05). SCG did not stimulate VSM growth in transwell cocultures. An antibody that neutralized the activity of transforming growth factor-β2 (TGF-β2) inhibited SCG stimulation of VSM growth in coculture. SCG stimulation of VSM growth was also inhibited by an endothelin A receptor antagonist. These data suggest novel mechanisms for sympathetic modulation of vascular growth that may play a role in the physiological and/or pathological growth of the vasculature.

Exogenous clustered neuropilin 1 enhances vasculogenesis and angiogenesis

Blood ◽  
2001 ◽  
Vol 97 (6) ◽  
pp. 1671-1678 ◽  
Author(s):  
Yoshihiro Yamada ◽  
Nobuyuki Takakura ◽  
Hirofumi Yasue ◽  
Hisao Ogawa ◽  
Hajime Fujisawa ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Low Dose ◽  
Vascular Development ◽  
Vegf Receptor ◽  
Wild Type ◽  
Flag Epitope ◽  
Neuropilin 1 ◽  
Vasculogenesis And Angiogenesis

Neuropilin 1 (NP-1) is a receptor for vascular endothelial growth factor (VEGF) 165 (VEGF165) and acts as a coreceptor that enhances VEGF165 function through tyrosine kinase VEGF receptor 2 (VEGFR-2). Transgenic overexpression of np-1results in an excess of capillaries and blood vessels and a malformed heart. Thus, NP-1 may have a key role in vascular development. However, how NP-1 regulates vascular development is not well understood. This study demonstrates how NP-1 can regulate vasculogenesis and angiogenesis in vitro and in vivo. In homozygous np-1mutant (np-1−/−) murine embryos, vascular sprouting was impaired in the central nervous system and pericardium. Para-aortic splanchnopleural mesoderm (P-Sp) explants fromnp-1−/− mice also had vascular defects in vitro. A monomer of soluble NP-1 (NP-1 tagged with Flag epitope) inhibited vascular development in cultured wild-type P-Sp explants by sequestering VEGF165. In contrast, a dimer of soluble NP-1 (NP-1 fused with the Fc part of human IgG) enhanced vascular development in cultured wild-type P-Sp explants. Moreover, the NP-1–Fc rescued the defective vascular development in culturednp-1−/− P-Sp explants. A low dose of VEGF alone did not promote phosphorylation of VEGFR-2 on endothelial cells from np-1−/− embryos, but simultaneous addition of a low dose of VEGF and NP-1–Fc phosphorylated VEGFR-2 significantly. Moreover, NP-1–Fc rescued the defective vascularity of np-1−/− embryos in vivo. These results suggest that a dimer form of soluble NP-1 delivers VEGF165 to VEGFR-2–positive endothelial cells and promotes angiogenesis.

Enhancement of the response to levodopa therapy after intrastriatal transplantation of autologous sympathetic neurons in patients with Parkinson disease

2001 ◽  
Vol 95 (2) ◽  
pp. 275-284 ◽  
Author(s):  
Naoyuki Nakao ◽  
Koji Kakishita ◽  
Yuji Uematsu ◽  
Tatsuya Yoshimasu ◽  
Toshiya Bessho ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Sympathetic Ganglion ◽  
Ethical Issues ◽  
Sympathetic Neurons ◽  
Performance Status ◽  
Sympathetic Neuron ◽  
Content Type ◽  
Intracerebral Transplantation ◽  
Fine Print

Object. There is growing evidence to indicate that tissue transplantation can potentially be a restorative neurosurgical treatment for patients with Parkinson disease (PD). In this study the authors investigated the clinical effect of unilateral intrastriatal grafting of autologous sympathetic neurons in patients with PD. Methods. Four patients with PD who had been observed for 1 year after graft placement of autologous sympathetic neurons were selected for an analysis of the effect of that procedure. Sympathetic ganglion tissue was endoscopically excised from the thoracic sympathetic trunk and grafted into the unilateral caudate head and putamen of the PD patients. No changes were made in the patients' preoperative regimens of antiparkinsonian medications, and clinical evaluations were made principally according to those established by the Core Assessment Program for Intracerebral Transplantation Committee. Whereas the sympathetic neuron grafts failed to affect clinical scores reflecting the patients' motor performance, which was evaluated during either the “on” or “off” phases, the grafts significantly increased the duration of the levodopa-induced on period with consequent reduction in the percentage of time spent in the off phase. This beneficial effect may be explained by the results of the present in vitro experiment, which show that human sympathetic neurons have the ability to convert exogenous levodopa to dopamine and to store this synthesized dopamine. Conclusions. Sympathetic neuron autografts were found to improve performance status in patients with PD by reducing the time spent in the off phase. This clearly indicates that sympathetic ganglion tissue, the use of which involves few ethical issues, can be an efficacious donor source in cell transplantation therapy for PD. Further studies are needed to determine whether the grafts may provide long-lasting clinical benefits.

The behaviour in vitro of epidermal cells from normal and pupoid foetus mutant mouse embryos

1985 ◽  
Vol 79 (1) ◽  
pp. 305-315
Author(s):  
S. Anderson ◽  
D.A. Ede
Keyword(s):  
Mutant Mouse ◽  
Cell Mass ◽  
Time Lapse ◽  
Epidermal Cells ◽  
Mouse Embryos ◽  
Sensory Nerves ◽  
Recessive Lethal Mutation ◽  
Mutant Mouse Embryos ◽  
Peripheral Sensory

Pupoid foetus (pf/pf) is a recessive lethal mutation of the mouse causing epidermal hypertrophy and disorganization of peripheral sensory nerves and mesoderm. The comparative behaviour of epidermal cells from normal and pupoid foetus mutant mouse embryos was studied in vitro. Epidermal explants from the snout region of 12.5- to 13-day embryos were grown in culture for periods of up to 2 weeks. Cultures from both phenotypes were filmed using time-lapse cinemicrography for up to 3 days following explantation. Paths of individual cells were traced as they migrated from the explant, and their rate of locomotion and directional persistence were calculated. Differences in these parameters between the two phenotypes were tested statistically. The overall morphology of the cultures, and the tendency of the cells to detach from the periphery of the cell mass were also compared. The results show that, between 25 and 60 h after explantation, epidermal cells from pupoid foetus embryos move consistently more slowly than normal cells, and follow a more erratic path. This situation is reversed, however, between 16 and 25 h. This suggests that the pf mutation causes an alteration in epidermal cells that affects their locomotion, and which is maintained for a minimum of 3 days in the absence of other influencing factors.

Heightened activation of embryonic megakaryocytes causes aneurysms in the developing brain of mice lacking podoplanin

Blood ◽  
2021 ◽  
Author(s):  
Christopher Michael Hoover ◽  
Yuji Kondo ◽  
Bojing Shao ◽  
Michael McDaniel ◽  
Robert Lee ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Platelet Activation ◽  
Mutant Mouse ◽  
Neural Tissue ◽  
Mouse Embryos ◽  
Wild Type ◽  
Primitive Hematopoiesis ◽  
Mutant Mouse Embryos ◽  
Granule Release ◽  
Angiopoietin 1

During early embryonic development in mammals, including humans and mice, megakaryocytes first originate from primitive hematopoiesis in the yolk sac. These embryonic megakaryocytes (eMk) circulate in the vasculature with unclear function. Here we report that podoplanin (PDPN), the ligand of C-type lectin-like receptor (CLEC-2) on megakaryocytes/platelets, is temporarily expressed in neural tissue during midgestation in mice. Loss of PDPN or CLEC-2 resulted in aneurysms and spontaneous hemorrhage specifically in the lower diencephalon during midgestation. Surprisingly, more eMks/platelets had enhanced granule release and localized to lower diencephalon in mutant mouse embryos than wild-type littermates prior to hemorrhage. We found that PDPN counteracted the collagen I-induced secretion of angiopoietin-1 from fetal megakaryocytes, which coincided with enhanced TIE2 activation in aneurysm-like sprouts of PDPN-deficient embryos. Blocking platelet activation prevented the PDPN-deficient embryo from developing vascular defects. Our data reveal a new role for PDPN in regulating eMk function during midgestation.

scholarly journals Neuropilin ligands in vascular and neuronal patterning

2009 ◽  
Vol 37 (6) ◽  
pp. 1228-1232 ◽  
Author(s):  
Alessandro Fantin ◽  
Charlotte H. Maden ◽  
Christiana Ruhrberg
Keyword(s):  
Blood Vessels ◽  
Transmembrane Protein ◽  
Sympathetic Neurons ◽  
Neural Crest Cell ◽  
Sensory Nerves ◽  
Surface Receptors ◽  
Neuropilin 1 ◽  
Pharyngeal Arch Arteries ◽  
Vessel Development

Blood vessels and neurons share guidance cues and cell-surface receptors to control their behaviour during embryogenesis. The transmembrane protein NRP1 (neuropilin 1) is present on both blood vessels and nerves and binds two structurally diverse ligands, the class 3 semaphorin SEMA3A and an isoform of the vascular endothelial growth factor VEGF-A termed VEGF165 (VEGF164 in mice). In vitro, SEMA3A competes with VEGF164 for binding to NRP1 to modulate the migration of endothelial cells and neuronal progenitors. It was therefore hypothesized that NRP1 signalling controls neurovascular co-patterning by integrating competing VEGF164 and SEMA3A signals. However, SEMA3A, but not VEGF164, is required for axon patterning of motor and sensory nerves, and, vice versa, VEGF164 rather than SEMA3A is required for blood vessel development. Ligand competition for NRP1 therefore does not explain neurovascular congruence. Instead, these ligands control different aspects of neurovascular patterning that have an impact on cardiovascular function. Thus SEMA3A/NRP1 signalling guides the NCC (neural crest cell) precursors of sympathetic neurons as well as their axonal projections. In addition, VEGF164 and a second class 3 semaphorin termed SEMA3C contribute to the remodelling of the embryonic pharyngeal arch arteries and primitive heart outflow tract by acting on endothelium and NCCs respectively. Consequently, loss of either of these NRP1 ligands disrupts blood flow into and out of the heart. Multiple NRP1 ligands therefore co-operate to orchestrate cardiovascular morphogenesis.

p-Aminobenzamidine-sensitive acrosomal protease(s) other than acrosin serve the sperm penetration of the egg zona pellucida in mouse

Zygote ◽  
1998 ◽  
Vol 6 (4) ◽  
pp. 311-319 ◽  
Author(s):  
Kazuo Yamagata ◽  
Keitaro Murayama ◽  
Nobuhisa Kohno ◽  
Shin-ichi Kashiwabara ◽  
Tadashi Baba
Keyword(s):  
Zona Pellucida ◽  
Mutant Mouse ◽  
Significant Inhibition ◽  
Wild Type ◽  
Significant Delay ◽  
Chloromethyl Ketone ◽  
Diisopropyl Fluorophosphate ◽  
Sperm Suspension ◽  
Sperm Penetration

It has been reported that a significant delay in protein dispersal from the acrosomal matrix is observed in wild-type sperm by adding p-aminobenzamidine, a trypsin/acrosin inhibitor, to the incubation medium. The pattern of this delayed release was similar to that of the acrosin-deficient mutant mouse sperm (Yamagata et al., J. Biol. Chem., 273, 10470–4, 1998). In the present study, no further delay in protein dispersal was found when the acrosin-deficient sperm were treated with p-aminobenzamidine, indicating that among the p-aminobenzamidine-sensitive protease(s) only acrosin may function to accelerate this process. Although the acrosin-deficient sperm penetrated the zona pellucida (Baba et al., J. Biol. Chem., 269, 31845–9, 1994), the addition of p-aminobenzamidine to the fertilisation medium caused a significant inhibition of fertilisation in vitro. This indicates that there is a p-aminobenzamidine-sensitive protease(s) other than acrosin participating in the zona penetration step. Indeed, we demonstrated that a non-acrosin protease with a size of 42 kDa was present in the supernatant of the acrosome-reacted sperm suspension. The enzyme was inhibited by p-amimobenzamidine, diisopropyl fluorophosphate and Nα-tosyl-L-lysine chloromethyl ketone, and was apparently activated by acrosin.

scholarly journals ISKpn40-Mediated Mobilization of the Colistin Resistance Gene mcr-3.11 in Escherichia coli

2020 ◽  
Vol 64 (10) ◽  
Author(s):  
Yu-Zhang He ◽  
Teng-Fei Long ◽  
Cai-Ping Chen ◽  
Bing He ◽  
Xing-Ping Li ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Gene ◽  
Wild Type ◽  
Colistin Resistance ◽  
Content Type ◽  
First Report ◽  
E Coli ◽  
Target Sites

ABSTRACT The mobile colistin resistance gene mcr-3 has globally disseminated since it was first reported in 2017 in Escherichia coli. In vitro mobilization assays in this study demonstrate the functionality of the composite transposon structure ISKpn40-mcr-3.11-dgkA-ISKpn40 in wild-type and recA− E. coli strains. These transpositions generated 4-bp duplications at the target sites. This is the first report demonstrating the mobility of the mcr-3.11 gene by transposition.

The transcription factor dHAND is a downstream effector of BMPs in sympathetic neuron specification

Development ◽  
2000 ◽  
Vol 127 (18) ◽  
pp. 4073-4081 ◽  
Author(s):  
M.J. Howard ◽  
M. Stanke ◽  
C. Schneider ◽  
X. Wu ◽  
H. Rohrer
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Proteins ◽  
Sympathetic Neurons ◽  
Sympathetic Neuron ◽  
Sympathetic Ganglia ◽  
Catecholaminergic Neurons ◽  
Helix Loop Helix ◽  
Downstream Effector

The dHAND basic helix-loop-helix transcription factor is expressed in neurons of sympathetic ganglia and has previously been shown to induce the differentiation of catecholaminergic neurons in avian neural crest cultures. We now demonstrate that dHAND expression is sufficient to elicit the generation of ectopic sympathetic neurons in vivo. The expression of the dHAND gene is controlled by bone morphogenetic proteins (BMPs), as suggested by BMP4 overexpression in vivo and in vitro, and by noggin-mediated inhibition of BMP function in vivo. The timing of dHAND expression in sympathetic ganglion primordia, together with the induction of dHAND expression in response to Phox2b implicate a role for dHAND as transcriptional regulator downstream of Phox2b in BMP-induced sympathetic neuron differentiation.

Mice that lack astrotactin have slowed neuronal migration

Development ◽  
2002 ◽  
Vol 129 (4) ◽  
pp. 965-972 ◽  
Author(s):  
Niels C. Adams ◽  
Toshifumi Tomoda ◽  
Margaret Cooper ◽  
Gunnar Dietz ◽  
Mary E. Hatten
Keyword(s):  
Neuronal Migration ◽  
Abnormal Development ◽  
Wild Type ◽  
Migration Rates ◽  
Targeted Gene Disruption ◽  
Cell Assays ◽  
Cortical Regions ◽  
The Brain

The cortical regions of the brain are laminated as a result of directed migration of precursor cells along glia during development. Previously, we have used an assay system to identify astrotactin as a neuronal ligand for migration on glial fibers. To examine the function of astrotactin in vivo, we generated a null mutation by targeted gene disruption. The cerebella of astrotactin null mice are approximately 10% smaller than wild type. In vitro and in vivo cerebellar granule cell assays show a decrease in neuron-glial binding, a reduction in migration rates and abnormal development of Purkinje cells. Consequences of this are poorer balance and coordination. Thus, astrotactin functions in migration along glial processes in vivo, a process required for generating laminar structures and for the development of synaptic partner systems.

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