Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 1, Pages 125-132Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4472-07.2008
Keywords
Runx1; nociceptors; Mrg class G-protein-coupled receptors; nociceptive ion channels and receptors; cell type specification; dorsal root ganglia
Categories
Funding
- NIDCR NIH HHS [R01 DE013843, 1R01DE018025, R01 DE018025] Funding Source: Medline
- NINDS NIH HHS [P01 NS047572, P01 NS048499, 5P01NS047572, 5T32NS007473-09, T32 NS007473] Funding Source: Medline
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Mrg class G-protein-coupled receptors (GPCRs) are expressed exclusively in sensory neurons in the trigeminal and dorsal root ganglia. Pharmacological activation of Mrg proteins is capable of modulating sensory neuron activities and elicits nociceptive effects. In this study, we illustrate a control mechanism that allows the Runx1 runt domain transcription factor to generate compartmentalized expression of these sensory GPCRs. Expression of MrgA, MrgB, and MrgC subclasses is confined to an A/B/C neuronal compartment that expresses Runx1 transiently ( or does not express Runx1), whereas MrgD expression is restricted to a D compartment with persistent Runx1 expression. Runx1 is initially required for the expression of all Mrg genes. However, during late development Runx1 becomes a repressor for MrgA/B/C genes. As a result, MrgA/B/C expression persists only in the Runx1(-) A/B/C compartment. In Delta 446 mice, in which Runx1 lacks the C-terminal repression domain, expression of MrgA/B/C genes is dramatically expanded into the Runx1 (+) D compartment. MrgD expression, however, is resistant to Runx1-mediated repression in the D compartment. Therefore, the creation of Runx1(+) and Runx1 (-) compartments, in conjunction with different responses of Mrg genes to Runx1-mediated repression, results in the compartmentalized expression of MrgA/B/C versus MrgD genes. Within the MrgA/B/C compartment, MrgB4-expressing neurons innervate exclusively the hairy skin. Here we found that Smad4, a downstream component of bone morphological protein-mediated signaling, is required selectively for the expression of MrgB4. Our study suggests a new line of evidence that specification of sensory subtypes is established progressively during perinatal and postnatal development.
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