INT203473

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Context Info
Confidence 0.76
First Reported 2007
Last Reported 2010
Negated 3
Speculated 3
Reported most in Body
Documents 69
Total Number 72
Disease Relevance 25.94
Pain Relevance 11.36

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

nucleus (Pou4f1) DNA binding (Pou4f1)
Anatomy Link Frequency
neurons 9
retina 4
sensory neurons 4
spinal 3
retinal ganglion cell 3
Pou4f1 (Mus musculus)
Pain Link Frequency Relevance Heat
trigeminal ganglion 3720 100.00 Very High Very High Very High
Central nervous system 169 98.40 Very High Very High Very High
Nerve growth factor 32 97.44 Very High Very High Very High
midbrain 44 96.96 Very High Very High Very High
Glutamate 10 96.96 Very High Very High Very High
Neurotransmitter 97 96.92 Very High Very High Very High
Spinal cord 139 96.08 Very High Very High Very High
nociceptor 1024 95.72 Very High Very High Very High
gABA 65 95.52 Very High Very High Very High
5HT 20 89.16 High High
Disease Link Frequency Relevance Heat
Ganglion Cysts 4537 100.00 Very High Very High Very High
Targeted Disruption 1860 100.00 Very High Very High Very High
Death 102 99.62 Very High Very High Very High
Sprains And Strains 7 98.44 Very High Very High Very High
Repression 304 95.88 Very High Very High Very High
Optic Nerve Injuries 16 95.34 Very High Very High Very High
Retrograde Degeneration 8 94.48 High High
Neurodegenerative Disease 225 94.40 High High
Cytomegalovirus Infection 36 91.68 High High
Pain 126 88.20 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation

The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis.

Gene_expression (expressed) of pou4f1 in sensory neurons associated with ganglion cysts and trigeminal ganglion
1) Confidence 0.76 Published 2010 Journal Neural Dev Section Title Doc Link PMC2829025 Disease Relevance 0.59 Pain Relevance 0.32
In transgenic embryos expressing a Brn3a-VP16 dominant transactivator, Runx3 mRNA expression is increased, suggesting that it is a direct regulatory target of Brn3a.
Gene_expression (expressing) of Brn3a in embryos associated with targeted disruption
2) Confidence 0.76 Published 2010 Journal Neural Dev Section Abstract Doc Link PMC2829025 Disease Relevance 0.54 Pain Relevance 0.33
Brn3a-VP16 was expressed under control of an 11-kb Brn3a sensory enhancer/promoter, in which the native sequences mediating Brn3a binding have been mutated to eliminate negative autoregulation [21].


Gene_expression (expressed) of Brn3a
3) Confidence 0.76 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.09 Pain Relevance 0
Recombinant Brn3a protein was produced by transfecting HEK293 cells with a plasmid containing the full coding sequence of Brn3a in the vector pcDNA1-amp using Lipofectamine 2000 (Invitrogen).
Gene_expression (produced) of Brn3a
4) Confidence 0.76 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0 Pain Relevance 0
We found that Brn3a is co-expressed with the pan-sensory transcription factor Islet1 at this stage, although the relative signals for the two proteins vary (Figure 1A).
Gene_expression (expressed) of Brn3a
5) Confidence 0.76 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.34 Pain Relevance 0.14
Loss of Brn3a expression resulted in increased expression of essentially all of the anterior HoxA, HoxB and HoxC genes, and the changes reached statistical significance (p < 0.005 or p > 0.995, Materials and Methods) for seven genes in this group (Figure 5).
Gene_expression (expression) of Brn3a in anterior
6) Confidence 0.76 Published 2007 Journal Neural Develop Section Body Doc Link PMC1796875 Disease Relevance 0.22 Pain Relevance 0
Thus, 93% of green cells express Pou4f1.
Gene_expression (express) of Pou4f1
7) Confidence 0.70 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0
In mutants, only dI6 does not express Brn3a.
Neg (not) Gene_expression (express) of Brn3a
8) Confidence 0.70 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0
Brn3a regulates neuronal subtype specification in the trigeminal ganglion by promoting Runx expression during sensory differentiation

The transcription factor Brn3a, product of the pou4f1 gene, is expressed in most sensory neurons throughout embryogenesis.

Gene_expression (expressed) of Brn3a in sensory neurons associated with ganglion cysts and trigeminal ganglion
9) Confidence 0.66 Published 2010 Journal Neural Dev Section Title Doc Link PMC2829025 Disease Relevance 0.59 Pain Relevance 0.32
Thus, although the large Ret+/Runx1- neurons express Brn3a (Figure 1E), they do not require it for survival, or for Ret expression.


Gene_expression (express) of Brn3a in neurons
10) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.49 Pain Relevance 0.75
In Brn3a-/- embryos, TrkB- and TrkC-expressing neurons do not appropriately segregate into distinct populations, and Runx3 expression is not initiated (Figure 4F, H).
Gene_expression (expressing) of Brn3a in neurons
11) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.30 Pain Relevance 0.18
The normal initial expression of TrkC in Brn3a-/- TG suggests that regulation of TrkC is a secondary effect.
Gene_expression (expression) of Brn3a associated with trigeminal ganglion
12) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.28 Pain Relevance 0.16
These early Ret+ neurons do not co-express TrkA or Runx1, either in control or Brn3a-/- TG, and probably constitute a subset of mechanoreceptors [40].
Gene_expression (express) of Brn3a in mechanoreceptors associated with trigeminal ganglion
13) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.33 Pain Relevance 0.12
This expression cassette was placed downstream of regulatory sequences derived from the mouse Brn3a locus that have previously been shown to target expression specifically to sensory neurons throughout the neural axis [21].
Gene_expression (expression) of Brn3a in neural
14) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.22 Pain Relevance 0.07
Remarkably few genes show this relationship, suggesting that Brn3a functions primarily as a repressor at this stage.
Gene_expression (functions) of Brn3a
15) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.52 Pain Relevance 0.03
The abnormally persistent co-expression of TrkB and TrkC in the Brn3a-/- TG, and the subsequent loss of TrkC expression, are all consistent with effects mediated by Runx3.
Gene_expression (expression) of Brn3a associated with trigeminal ganglion
16) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.68 Pain Relevance 0.48
Further support for a role of Runx1 in restricting the expression of TrkB is derived from the observation that a small number of neurons that maintain Runx1 expression in the Brn3a knockout at E12.5 and E13.5 are TrkB negative (Figure 5D, H).
Gene_expression (knockout) of Brn3a in neurons associated with targeted disruption
17) Confidence 0.66 Published 2010 Journal Neural Dev Section Body Doc Link PMC2829025 Disease Relevance 0.59 Pain Relevance 0.10
Together these data show that Brn3a acts upstream of the Runx factors, which then repress TrkB expression to allow establishment of the non-overlapping Trk receptor profiles and correct terminally differentiated phenotypes.



Gene_expression (acts) of Brn3a
18) Confidence 0.66 Published 2010 Journal Neural Dev Section Abstract Doc Link PMC2829025 Disease Relevance 0.41 Pain Relevance 0.28
The LIM-domain transcription factor Islet1 is co-expressed with Brn3a in the sensory system [10], but in the CNS it is expressed primarily in motor neurons [28,29], and also has important roles in the development of the heart [30] and pancreatic islet cells [31].
Gene_expression (expressed) of Brn3a in sensory system associated with central nervous system
19) Confidence 0.66 Published 2007 Journal Neural Develop Section Body Doc Link PMC1796875 Disease Relevance 0.17 Pain Relevance 0.27
To understand the developmental programs regulated by Brn3a at spinal versus cranial levels, we next analyzed global gene expression in E13.5 DRG from Brn3a mutant embryos and wild-type controls.
Spec (analyzed) Gene_expression (expression) of Brn3a in embryos
20) Confidence 0.66 Published 2007 Journal Neural Develop Section Body Doc Link PMC1796875 Disease Relevance 0.29 Pain Relevance 0.17

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