Involvement of IKAP in Peripheral Target Innervation and in Specific JNK and NGF Signaling in Developing PNS Neurons

ABSTRACTFunctionally important regions of sensory maps are overrepresented in the sensory pathways and cortex, but the underlying developmental mechanisms are not clear. In the spinal cord dorsal horn (DH), we recently showed that paw innervating Mrgprd+ non-peptidergic nociceptors display distinctive central arbor morphologies that well correlate with increased synapse transmission efficiency and heightened sensitivity of distal limb skin. Given that peripheral and central arbor formation of Mrgprd+ neurons co-occurs around the time of birth, we tested whether peripheral cues from different skin areas and/or postnatal reorganization mechanisms could instruct this somatotopic difference among central arbors. We found that, while terminal outgrowth/refinement occurs during early postnatal development in both the skin and the DH, postnatal refinement of central terminals precedes that of peripheral terminals. Further, we used single-cell ablation of Ret to genetically disrupt epidermal innervation of Mrgprd+ neurons and revealed that the somatotopic difference among their central arbors was unaffected by this manipulation. Finally, we saw that region-specific Mrgprd+ central terminal arbors are present from the earliest postnatal stages, before skin terminals are evident. Together, our data indicate that region-specific organization of Mrgprd+ neuron central arbors develops independently of peripheral target innervation and is present shortly after initial central terminal formation, suggesting that either cell-intrinsic and/or DH local signaling may establish this somatotopic difference.

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154 Specific subtypes of cutaneous mechanoreceptors require neurotrophin-3 following peripheral target innervation

International Journal of Developmental Neuroscience ◽

10.1016/0736-5748(96)80343-1 ◽

1996 ◽

Vol 14 ◽

pp. 87-87 ◽

Cited By ~ 1

Author(s):

M.S. Airaksinen ◽

M. Koltzenburg ◽

G.R. Lewin ◽

Y. Masu ◽

C. Helbig ◽

...

Keyword(s):

Peripheral Target ◽

Cutaneous Mechanoreceptors ◽

Target Innervation ◽

Neurotrophin 3

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Effect of Oligodendroglial Microdomain Components on NGF Signaling

Klinische Neurophysiologie ◽

10.1055/s-2004-832159 ◽

2004 ◽

Vol 35 (03) ◽

Author(s):

M Schmitz ◽

S Klopfleisch ◽

S Kloeppner ◽

HH Althaus

Keyword(s):

Ngf Signaling

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Faculty Opinions recommendation of NGF-promoted axon growth and target innervation requires GITRL-GITR signaling.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1097678.555631 ◽

2008 ◽

Author(s):

Hartmut Wekerle

Keyword(s):

Axon Growth ◽

Target Innervation

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Acceleration of TAA-Induced Liver Fibrosis by Stress Exposure Is Associated with Upregulation of Nerve Growth Factor and Glycopattern Deviations

International Journal of Molecular Sciences ◽

10.3390/ijms22105055 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5055

Author(s):

Catalina Atorrasagasti ◽

Flavia Piccioni ◽

Sophia Borowski ◽

Irene Tirado-González ◽

Nancy Freitag ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Liver Fibrosis ◽

Signaling Pathway ◽

Liver Damage ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Nerve Growth ◽

Fibrotic Process ◽

Ngf Signaling

Liver fibrosis results from many chronic injuries and may often progress to cirrhosis and hepatocellular carcinoma (HCC). In fact, up to 90% of HCC arise in a cirrhotic liver. Conversely, stress is implicated in liver damage, worsening disease outcome. Hence, stress could play a role in disrupting liver homeostasis, a concept that has not been fully explored. Here, in a murine model of TAA-induced liver fibrosis we identified nerve growth factor (NGF) to be a crucial regulator of the stress-induced fibrogenesis signaling pathway as it activates its receptor p75 neurotrophin receptor (p75NTR), increasing liver damage. Additionally, blocking the NGF decreased liver fibrosis whereas treatment with recombinant NGF accelerated the fibrotic process to a similar extent than stress challenge. We further show that the fibrogenesis induced by stress is characterized by specific changes in the hepatoglycocode (increased β1,6GlcNAc-branched complex N-glycans and decreased core 1 O-glycans expression) which are also observed in patients with advanced fibrosis compared to patients with a low level of fibrosis. Our study facilitates an understanding of stress-induced liver injury and identify NGF signaling pathway in early stages of the disease, which contributes to the established fibrogenesis.

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Comprehensive analysis of IgA nephropathy expression profiles: identification of potential biomarkers and therapeutic agents

BMC Nephrology ◽

10.1186/s12882-021-02356-4 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alieh Gholaminejad ◽

Yousof Gheisari ◽

Sedigheh Jalali ◽

Amir Roointan

Keyword(s):

Iga Nephropathy ◽

Regulatory Network ◽

Target Genes ◽

Expression Profiles ◽

Gene Signature ◽

Gene Expression Omnibus ◽

Integrative Approach ◽

Potential Factors ◽

Ngf Signaling ◽

Underlying Mechanisms

Abstract Background IgA nephropathy (IgAN) is a kidney disease recognized by the presence of IgA antibody depositions in kidneys. The underlying mechanisms of this complicated disease are remained to be explored and still, there is an urgent need for the discovery of noninvasive biomarkers for its diagnosis. In this investigation, an integrative approach was applied to mRNA and miRNA expression profiles in PBMCs to discover a gene signature and novel potential targets/biomarkers in IgAN. Methods Datasets were selected from gene expression omnibus database. After quality control checking, two datasets were analyzed by Limma to identify differentially expressed genes/miRNAs (DEGs and DEmiRs). Following identification of DEmiR-target genes and data integration, intersecting mRNAs were subjected to different bioinformatic analyses. The intersecting mRNAs, DEmiRs, related transcription factors (from TRRUST database), and long-non coding RNAs (from LncTarD database) were used for the construction of a multilayer regulatory network via Cytoscape. Result “GSE25590” (miRNA) and “GSE73953” (mRNA) datasets were analyzed and after integration, 628 intersecting mRNAs were identified. The mRNAs were mainly associated with “Innate immune system”, “Apoptosis”, as well as “NGF signaling” pathways. A multilayer regulatory network was constructed and several hub-DEGs (Tp53, STAT3, Jun, etc.), DEmiRs (miR-124, let-7b, etc.), TFs (NF-kB, etc.), and lncRNAs (HOTAIR, etc.) were introduced as potential factors in the pathogenesis of IgAN. Conclusion Integration of two different expression datasets and construction of a multilayer regulatory network not only provided a deeper insight into the pathogenesis of IgAN, but also introduced several key molecules as potential therapeutic target/non-invasive biomarkers.

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On Why Objects Appear Smaller in the Visual Periphery

Psychological Science ◽

10.1177/0956797619892624 ◽

2019 ◽

Vol 31 (1) ◽

pp. 88-96 ◽

Cited By ~ 1

Author(s):

Wladimir Kirsch ◽

Roland Pfister ◽

Wilfried Kunde

Keyword(s):

Visual Field ◽

Visual System ◽

Structural Properties ◽

Spatial Attention ◽

Visuospatial Attention ◽

Peripheral Target ◽

Perceptual Distortion ◽

Visual Periphery ◽

Peripheral Location ◽

Exogenous Cue

An object appears smaller in the periphery than in the center of the visual field. In two experiments ( N = 24), we demonstrated that visuospatial attention contributes substantially to this perceptual distortion. Participants judged the size of central and peripheral target objects after a transient, exogenous cue directed their attention to either the central or the peripheral location. Peripheral target objects were judged to be smaller following a central cue, whereas this effect disappeared completely when the peripheral target was cued. This outcome suggests that objects appear smaller in the visual periphery not only because of the structural properties of the visual system but also because of a lack of spatial attention.

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