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 delta446 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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机译：Mrg类G蛋白偶联受体（GPCR）仅在三叉神经和背根神经节的感觉神经元中表达。 Mrg蛋白的药理激活能够调节感觉神经元活动并引起伤害性作用。在这项研究中，我们举例说明了一种控制机制，该机制允许Runx1矮级域转录因子生成这些感觉GPCR的间隔表达。 MrgA，MrgB和MrgC子类的表达仅限于瞬时表达Runx1（或不表达Runx1）的“ A / B / C”神经元区室，而MrgD表达仅限于具有持续Runx1表达的“ D”区室。最初需要Runx1来表达所有Mrg基因。但是，在后期发育期间，Runx1成为MrgA / B / C基因的阻遏物。结果，MrgA / B / C表达仅在Runx1-“ A / B / C”部分中持续存在。在Runx1缺少C端阻遏域的delta446小鼠中，MrgA / B / C基因的表达急剧扩展到Runx1 +“ D”区室。但是，MrgD表达对“ D”区室中Runx1介导的阻遏具有抗性。因此，Runx1 +和Runx1隔室的创建，结合Mrg基因对Runx1介导的阻遏的不同反应，导致MrgA / B / C与MrgD基因的分隔表达。在MrgA / B / C隔室中，表达MrgB4的神经元专门支配着毛状皮肤。在这里，我们发现Smad4，骨形态蛋白介导的信号传导的下游成分，是MrgB4表达所必需的。我们的研究提出了一条新的证据，表明围产期和产后发育过程中逐步建立了感觉亚型规范。
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