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Cell Subtype-specific Analysis of Neuronal Membrane Proteasome in Somatosensory Neurons
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The evolutionarily conserved transcription factor PRDM12 controls sensory neuron development and pain perception
Vanja Nagy1, Tiffany Cole, Claude Van Campenhout
1IMBA-Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria; UNSW Medicine, Sydney, Australia.
Cell Cycle (Georgetown, Tex.)
|April 21, 2015
Summary
PRDM12 is a crucial gene for sensory neuron development and pain perception. Its conserved function across species, including humans and flies, highlights its role in hereditary sensory and autonomic neuropathy.
Area of Science:
- Developmental Biology
- Neuroscience
- Genetics
Background:
- PRDM12 is a transcription factor family involved in cell fate.
- Hereditary Sensory and Autonomic Neuropathy (HSAN) is linked to PRDM12 mutations.
- Sensory neuron specification and pain perception are complex biological processes.
Purpose of the Study:
- To investigate the role of PRDM12 in sensory neuron development.
- To understand the evolutionary conservation of PRDM12 function.
- To identify downstream targets of PRDM12 in nociception.
Main Methods:
- Xenopus and Drosophila model systems were used.
- Human PRDM12 mutations were modeled and tested.
- Gene expression analysis and knockdown experiments were performed.
Main Results:
- PRDM12 is essential for sensory neuron specification in Xenopus.
- Human PRDM12 mutations impair sensory neuronal marker expression.
- The Drosophila homolog, Hamlet, regulates nociceptive behavior.
- TRHDE was identified as a downstream target affecting nociception.
Conclusions:
- PRDM12 and its homolog Hamlet are conserved master regulators of sensory neuron development.
- PRDM12 plays a critical role in pain perception and nociception.
- Novel pathways regulating nociception were uncovered across species.
Keywords:
BSA, bovine serum albuminBrn3d, brain 3dCGNL1, cyclin L1ChIP, chromatin immunoprecipitationDAPI, 4′,6-diamidino-2-phenylindoleDDK, DYKDDDDK epitopeDrgx, dorsal root ganglia homeoboxECL, enhanced chemiluminescenceEn1, engrailed-1FDR, false discovery rateFPKM, fragments per kilobase exonGAPDH, glyceraldehyde 3-phospate dehydrogenaseGEO, gene expression omnibusGFP, green fluorescent proteinHEK293, human embryonic kidney cell 293HRP, horseraddish peroxidaseHSAN, hereditary and sensory autonomic neuropathyHamletHmx3, H6 family homeobox 3IL1R1, interleukin 1 receptor type 1MO, morpholino oligonucleotideNBT/BCIP, nitro blue tetrazolium / 5-bromo-4-chloro-3-indolyl-phosphatePBS, phosphate buffered salinePDB, protein data basePMID, pubmed identification.PRDM12PRDM12, PR homology domain-containing member 12RA, retinoic acidRT-qPCR, real-time quantitative polymerase chain reactionS1PR1, Sphi8ngosine-1-phosphate receptor 1SET, Su(var)3–9 and ‘Enhancer of zeste’Sncg, Synuclein Gamma (Breast Cancer-Specific Protein 1)TRH(DE), tryrotropin-releasing hormone degrading enzymeTRHDETRHDE, tyrotropin-releasing hormone degrading enzymeTlx3, T-cell leukemia homeobox 3nociceptionpCMV6, plasmid cytomegalovirussensory neuronsRelated Concept Videos
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