Lu Qi<\/a>,\u00a0Chengcheng Huang<\/a>,\u00a0Xiaohua Wu<\/a>,\u00a0Yeqi Tao<\/a>,\u00a0Jingjing Yan<\/a>,\u00a0Tianyong Shi<\/a>,\u00a0Cheng Cao<\/a>,\u00a0Lu Han<\/a>,\u00a0Mengsheng Qiu<\/a>,\u00a0Qiufu Ma<\/a>,\u00a0Zijing Liu<\/a>\u00a0<\/sup>,\u00a0Yang Liu<\/a>\u00a0<\/sup><\/p>\n\n\n\n The Journal of Neuroscience, May 31, 2017<\/strong><\/p>\n\n\n\n The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch, and others. Recent genetic and single-cell RNA sequencing studies have revealed a group of DRG neurons that could be particularly relevant for acute and chronic itch information transmission. They express the natriuretic peptide type B (NPPB), as well as a cohort of receptors and neuropeptides that have been implicated in chronic itch manifestation, including the interleukin-31 receptor A (IL-31ra) and its coreceptor oncostatin M receptor (Osmr), the cysteinyl leukotriene receptor 2 (Cysltr2), somatostatin, and neurotensin. However, how these neurons are generated during development remains unclear. Here we report that Runx1 is required to establish all these molecular features of NPPB+<\/sup>\u00a0neurons. We further show that while early embryonic Runx1 activity is required for the formation of NPPB+<\/sup>\u00a0cells, at later stages Runx1 switches to a genetic repressor and thus its downregulation becomes a prerequisite for the proper development of these pruriceptors. This mode by Runx1 is analogous to that in controlling another group of pruriceptors that specifically express the chloroquine receptor MrgprA3. Finally, behavioral studies using both sexes of mice revealed marked deficits in processing acute and chronic itch in\u00a0Runx1<\/em>\u00a0conditional knock-out mice, possibly attributable to impaired development of various pruriceptors.<\/p>\n\n\n\n SIGNIFICANCE STATEMENT<\/strong>\u00a0<\/p>\n\n\n\n Our studies reveal a generalized control mode by Runx1 for pruriceptor development and consolidate a hierarchical control mechanism for the formation of sensory neurons transmitting distinct modalities. Among dorsal root ganglion neurons that initially express the neurotrophin receptor TrkA, Runx1 is necessary for the proper development of those neurons that innervate tissues derived from the ectoderm such as skin epidermis and hair follicles. These Runx1-dependent cutaneous sensory neurons are then divided into two groups based on persistent or transient Runx1 expression. The Runx1-persistent group is involved in transmitting mechanical and thermal information, whereas the Runx1-transient group transmits pruriceptive information. Such hierarchical control mechanisms may provide a developmental solution for the formation of sensory circuits that transmit distinct modalities.<\/p>\n\n\n\n Keywords:\u00a0<\/strong>NPPB; Runx1; chronic itch; development; pruriceptor; transcriptional regulation.<\/p>\n\n\n\n <\/p>\n","protected":false},"excerpt":{"rendered":" Hierarchical Specification of Pruriceptors by Runt-Domain Transcription Factor Runx1 Lu Qi,\u00a0Chengcheng Huang,\u00a0Xiaohua Wu,\u00a0Yeqi Tao,\u00a0Jingjing Yan,\u00a0Tianyong Shi,\u00a0Cheng Cao,\u00a0Lu Han,\u00a0Mengsheng Qiu,\u00a0Qiufu Ma,\u00a0Zijing Liu\u00a0,\u00a0Yang Liu\u00a0 The Journal of Neuroscience, May 31, 2017 Abstract The somatic sensory neurons in dorsal root ganglia (DRG) detect and transmit a diverse array of sensory modalities, such as pain, itch, cold, warm, touch, […]<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}}},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2295"}],"collection":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2295"}],"version-history":[{"count":1,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2295\/revisions"}],"predecessor-version":[{"id":2297,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=\/wp\/v2\/posts\/2295\/revisions\/2297"}],"wp:attachment":[{"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2295"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2295"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/misterx95.myds.me\/wordpress\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2295"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Abstract<\/h2>\n\n\n\n