title: Mechanisms of compartmentalized expression of Mrg class G-protein-coupled sensory receptors.
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 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.
authors.affiliation: Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Fu-Chia
authors.initials: FC
authors.lastname: Yang
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Okuda
authors.forename: Xinzhong
authors.initials: X
authors.lastname: Dong
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Zylka
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Chen
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
authors.forename: Rohini
authors.initials: R
authors.lastname: Kuner
authors.forename: Qiufu
authors.initials: Q
authors.lastname: Ma
mesh_terms: D000818:Animals; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D051901:Smad4 Protein / Q000235:genetics; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D043562:Receptors, G-Protein-Coupled; C493726:Runx1 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse