title: Genetic control of the segregation of pain-related sensory neurons innervating the cutaneous versus deep tissues.
abstract: Mammalian pain-related sensory neurons are derived from TrkA lineage neurons located in the dorsal root ganglion. These neurons project to peripheral targets throughout the body, which can be divided into superficial and deep tissues. Here, we find that the transcription factor Runx1 is required for the development of many epidermis-projecting TrkA lineage neurons. Accordingly, knockout of Runx1 leads to the selective loss of sensory innervation to the epidermis, whereas deep tissue innervation and two types of deep tissue pain are unaffected. Within these cutaneous neurons, Runx1 suppresses a large molecular program normally associated with sensory neurons that innervate deep tissues, such as muscle and visceral organs. Ectopic expression of Runx1 in these deep sensory neurons causes a loss of this molecular program and marked deficits in deep tissue pain. Thus, this study provides insight into a genetic program controlling the segregation of cutaneous versus deep tissue pain pathways.
authors: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Fu-Chia
authors: FC
authors: Yang
authors: Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Taralyn
authors: T
authors: Tan
authors: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Tianwen
authors: T
authors: Huang
authors: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors: Julie
authors: J
authors: Christianson
authors: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Omar A
authors: OA
authors: Samad
authors: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: Yang
authors: Y
authors: Liu
authors: Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA.
authors: David
authors: D
authors: Roberson
authors: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
authors: Brian M
authors: BM
authors: Davis
authors: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA; Department of Neurobiology, Harvard Medical School, 450 Brookline Avenue, Boston, MA 02115, USA. Electronic address: qiufu_ma@dfci.harvard.edu.
authors: Qiufu
authors: Q
authors: Ma
mesh_terms: D000818:Animals; D002460:Cell Line; D019070:Cell Lineage; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004817:Epidermis / Q000294:innervation*; D005727:Ganglia, Spinal / Q000166:cytology* / Q000502:physiology; D051379:Mice; D009132:Muscles / Q000294:innervation*; D009154:Mutation; D059226:Nociceptive Pain / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D014781:Viscera / Q000294:innervation
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse; D020917:Receptor, trkA