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The Journal of Neuroscience, January 2, 2008, 28(1):125-132; doi:10.1523/JNEUROSCI.4472-07.2008
Previous Article | Next Article
Development/Plasticity/Repair
Mechanisms of Compartmentalized Expression of Mrg Class G-Protein-Coupled Sensory Receptors
Yang Liu,1 Fu-Chia Yang,1 Tsukasa Okuda,2 Xinzhong Dong,3 Mark J. Zylka,4 Chih-Li Chen,5 David J. Anderson,6 Rohini Kuner,7 andQiufu Ma1 1Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, 2Department of Biochemistry and Molecular Biology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan, 3Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, 4Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, 5School of Medicine, Fu-Jen Catholic University, Taipei 24205, Taiwan, 6Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, and 7Department of Molecular Pharmacology, Pharmacology Institute, University of Heidelberg, Heidelberg 69120, Germany
Correspondence should be addressed to Qiufu Ma, Dana-Farber Cancer Institute, 1 Jimmy Fund Way, Boston, MA 02115. Email: qiufu_ma{at}dfci.harvard.edu
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
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.
Key words: Runx1; nociceptors; Mrg class G-protein-coupled receptors; nociceptive ion channels and receptors; cell type specification; dorsal root ganglia
Received June 5, 2007; revised Nov. 9, 2007; accepted Nov. 14, 2007.
Correspondence should be addressed to Qiufu Ma, Dana-Farber Cancer Institute, 1 Jimmy Fund Way, Boston, MA 02115. Email: qiufu_ma{at}dfci.harvard.edu
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