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Mechanisms of Compartmentalized Expression of Mrg Class G-Protein-Coupled Sensory Receptors

Liu, Yang and Yang, Fu-Chia and Okuda, Tsukasa and Dong, Xinzhong and Zylka, Mark J. and Chen, Chih-Li and Anderson, David J. and Kuner, Rohini and Ma, Qiufu (2008) Mechanisms of Compartmentalized Expression of Mrg Class G-Protein-Coupled Sensory Receptors. Journal of Neuroscience, 28 (1). pp. 125-132. ISSN 0270-6474. PMCID PMC6671167. https://resolver.caltech.edu/CaltechAUTHORS:20150306-094944495

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1523/JNEUROSCI.4472-07.2008DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6671167PubMed CentralArticle
ORCID:
AuthorORCID
Liu, Yang0000-0002-8155-9134
Anderson, David J.0000-0001-6175-3872
Additional Information:© 2008 Society for Neuroscience. Received June 5, 2007; revised Nov. 9, 2007; accepted Nov. 14, 2007. The work was supported by National Institutes of Health (NIH)–National Institute of Neurological Disorders and Stroke Training Grant 5T32NS007473-09 (F.-C.Y.), NIH–National Institute of Dental and Craniofacial Research Grant 1R01DE018025 (Q.M.), and NIH–National Institute of Neurological Disorders and Stroke Grant 5P01NS047572 (Q.M.). Q.M. is a Claudia Adams Barr Scholar. We thank Drs. Gary Gilliland and Nancy Speck for the Runx1 conditional knock-out mice, Chuxia Deng for conditional Smad4 null mice, David Rowitch for Wnt1-Cre mice, Tom Jessell for the Runx1 antibody, and Keith Ligon for critical comments on this manuscript.
Funders:
Funding AgencyGrant Number
NIH Predoctoral Fellowship5T32NS007473-09
NIH1R01DE018025
NIH5P01NS047572
Subject Keywords:Runx1; nociceptors; Mrg class G-protein-coupled receptors; nociceptive ion channels and receptors; cell type specification; dorsal root ganglia
Issue or Number:1
PubMed Central ID:PMC6671167
Record Number:CaltechAUTHORS:20150306-094944495
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150306-094944495
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:55584
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:06 Mar 2015 21:06
Last Modified:09 Mar 2020 13:19

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