INT103362

Context Info Confidence 0.78 First Reported 2002 Last Reported 2008 Negated 4 Speculated 0 Reported most in Body Documents 3 Total Number 31 Disease Relevance 0.14 Pain Relevance 0.81

cell differentiation (Lbx1) nucleus (Lbx1) DNA binding (Lbx1)

Anatomy Link Frequency dorsal 2 neural tubes 1 ventricular zone 1 limb muscle 1 neuronal 1 Lbx1 (Mus musculus)

Pain Link Frequency Relevance Heat interneuron 2 97.24 substantia gelatinosa 60 94.84 Spinal cord 64 94.44 Dorsal horn 4 77.36 Pain 31 66.24 Central nervous system 29 48.88 nociceptor 6 25.00 Dorsal horn neuron 29 24.36

Disease Link Frequency Relevance Heat Targeted Disruption 174 70.52 Pain 31 66.24 Apoptosis 58 43.44 Acquired Immune Deficiency Syndrome Or Hiv Infection 29 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Lbx1 is expressed in and required for the correct specification of three early dorsal interneuron populations and late-born neurons that form the substantia gelatinosa.

Gene_expression (expressed) of Lbx1 in substantia gelatinosa associated with substantia gelatinosa and interneuron

1) Confidence 0.78 Published 2002 Journal Neuron Section Abstract Doc Link 12062038 Disease Relevance 0 Pain Relevance 0.34

During development, these two major neuronal classes are delineated by the expression of the homeodomain transcription factor Lbx1.

Gene_expression (expression) of Lbx1 in neuronal

2) Confidence 0.78 Published 2002 Journal Neuron Section Abstract Doc Link 12062038 Disease Relevance 0 Pain Relevance 0.33

Similarly, most of the genes in Table 2 appeared to be expressed within the zone of Lbx1 expression, consistent with the idea that they are activated by Lbx1.

Gene_expression (expression) of Lbx1

3) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Approximately 20% of the analyzed cells came from early populations (dI4-dI6) and had therefore expressed Lbx1 for more than 24 hours, which may be sufficient for secondary target regulation.

Gene_expression (expressed) of Lbx1

4) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Heterozygous versus mutant comparisons gave markedly different results in green cells (Fig. 2A), which represent populations that normally express Lbx1, and white cells (Fig. 2B), which represent populations that normally do not express Lbx1.

Gene_expression (express) of Lbx1

5) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Thus, it is even possible that some of these target genes function in limb muscle precursors, which also express Lbx1.

Gene_expression (express) of Lbx1 in limb muscle

6) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Given that the set of Lbx1 targets differs between known populations, it is reasonable to assume that each network state in which Lbx1 is expressed has a different set of Lbx1 targets.

Gene_expression (expressed) of Lbx1

7) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

The genes corresponding to these probe sets were not included in the tables, but potentially have Lbx1-dependent expression.

Gene_expression (expression) of Lbx1-dependent

8) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Most of the genes in Table 1 appeared to be expressed outside of the zone of Lbx1 expression, consistent with the idea that they are repressed by Lbx1.

Gene_expression (expression) of Lbx1

9) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Thus, comparisons between mutant and heterozygous sources preferentially reveal immediate molecular consequences of Lbx1 expression, rather than delayed secondary effects.

Gene_expression (expression) of Lbx1

10) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

The homeodomain transcription factor Lbx1 is expressed in five such populations and loss of Lbx1 leads to distinct respecifications in each of the five populations.

Gene_expression (expressed) of Lbx1

11) Confidence 0.75 Published 2008 Journal PLoS ONE Section Abstract Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Heterozygous versus mutant comparisons gave markedly different results in green cells (Fig. 2A), which represent populations that normally express Lbx1, and white cells (Fig. 2B), which represent populations that normally do not express Lbx1.

Neg (not) Gene_expression (express) of Lbx1

12) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Second, these two populations have expressed Lbx1, or GFP, for less than 24 hours.

Gene_expression (expressed) of Lbx1

13) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Approximately 80% of Lbx1 expressing neurons in E12.5 neural tubes belong to the two late populations.

Gene_expression (expressing) of Lbx1 in neural tubes

14) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

In contrast, little scatter from the unity line was observed in the white cell comparison, indicating that few SSTF genes are regulated in cells where Lbx1 is not expressed.

Neg (not) Gene_expression (expressed) of Lbx1

15) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

Foxd3 and Isl1 are normally expressed in postmitotic populations that do not express Lbx1.

Neg (not) Gene_expression (express) of Lbx1

16) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

They are normally not expressed in any of the Lbx1 expressing populations.

Gene_expression (expressing) of Lbx1

17) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

The significant increase in the expression levels of these Hox genes in Lbx1 mutants indicates that Lbx1 represses the expression of these Hox genes in at least some dorsal cell populations.

Gene_expression (expression) of Lbx1 in dorsal

18) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0.07 Pain Relevance 0.11

The probe set for Lhx5 produced a robust, but Lbx1-independent, signal.

Gene_expression (produced) of Lbx1

19) Confidence 0.75 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0.03

Given that the set of Lbx1 targets differs between known populations, it is reasonable to assume that each network state in which Lbx1 is expressed has a different set of Lbx1 targets.

Gene_expression (targets) of Lbx1

20) Confidence 0.65 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2527684 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.