Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors

Yang Liu, Fu Chia Yang, Tsukasa Okuda, Xinzhong Dong, Mark J. Zylka, Chih Li Chen, David J. Anderson, Rohini Kuner, Qiufu Ma

Research output: Contribution to journalArticle

Abstract

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 Δ446 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.

Original languageEnglish (US)
Pages (from-to)125-132
Number of pages8
JournalJournal of Neuroscience
Volume28
Issue number1
DOIs
StatePublished - Jan 2 2008

Keywords

  • Cell type specification
  • Dorsal root ganglia
  • Mrg class G-protein-coupled receptors
  • Nociceptive ion channels and receptors
  • Nociceptors
  • Runx1

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors'. Together they form a unique fingerprint.

  • Cite this

    Liu, Y., Yang, F. C., Okuda, T., Dong, X., Zylka, M. J., Chen, C. L., Anderson, D. J., Kuner, R., & Ma, Q. (2008). Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors. Journal of Neuroscience, 28(1), 125-132. https://doi.org/10.1523/JNEUROSCI.4472-07.2008