Document Detail


Runx1 controls terminal morphology and mechanosensitivity of VGLUT3-expressing C-mechanoreceptors.
MedLine Citation:
PMID:  23325226     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs) are proposed to mediate pleasant touch and/or pain, but the molecular programs controlling C-LTMR development are unknown. Here, we performed genetic fate mapping, showing that VGLUT3 lineage sensory neurons are divided into two groups, based on transient or persistent VGLUT3 expression. VGLUT3-transient neurons are large- or medium-diameter myelinated mechanoreceptors that form the Merkel cell-neurite complex. VGLUT3-persistent neurons are small-diameter unmyelinated neurons that are further divided into two subtypes: (1) tyrosine hydroxylase (TH)-positive C-LTMRs that form the longitudinal lanceolate endings around hairs, and (2) TH-negative neurons that form epidermal-free nerve endings. We then found that VGLUT3-persistent neurons express the runt domain transcription factor Runx1. Analyses of mice with a conditional knock-out of Runx1 in VGLUT3 lineage neurons demonstrate that Runx1 is pivotal to the development of VGLUT3-persistent neurons, such as the expression of VGLUT3 and TH and the formation of the longitudinal lanceolate endings. Furthermore, Runx1 is required to establish mechanosensitivity in C-LTMRs, by controlling the expression of the mechanically gated ion channel Piezo2. Surprisingly, both acute and chronic mechanical pain was largely unaffected in these Runx1 mutants. These findings appear to argue against the recently proposed role of VGLUT3 in C-LTMRs in mediating mechanical hypersensitivity induced by nerve injury or inflammation. Thus, our studies provide new insight into the genetic program controlling C-LTMR development and call for a revisit for the physiological functions of C-LTMRs.
Authors:
Shan Lou; Bo Duan; Linh Vong; Bradford B Lowell; Qiufu Ma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-17     Completed Date:  2013-04-01     Revised Date:  2013-07-18    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  870-82     Citation Subset:  IM    
Affiliation:
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Transport Systems, Acidic / genetics,  metabolism*
Animals
Behavior, Animal / drug effects
Capsaicin / pharmacology
Core Binding Factor Alpha 2 Subunit / genetics,  metabolism*
Hyperalgesia / chemically induced,  genetics,  metabolism*
Ion Channels / genetics,  metabolism
Mechanoreceptors / physiology*
Mice
Mice, Knockout
Nerve Endings / physiology*
Neuralgia / chemically induced,  genetics,  metabolism*
Physical Stimulation
Skin / innervation
Tyrosine 3-Monooxygenase / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
P01 NS047572/NS/NINDS NIH HHS; P01 NS047572/NS/NINDS NIH HHS; P30 DK046200/DK/NIDDK NIH HHS; R01 DE018025/DE/NIDCR NIH HHS; R01 DE018025/DE/NIDCR NIH HHS; R01 DK075632/DK/NIDDK NIH HHS; R01 DK075632/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Amino Acid Transport Systems, Acidic; 0/Core Binding Factor Alpha 2 Subunit; 0/Ion Channels; 0/Piezo2 protein, mouse; 0/vesicular glutamate transporter 3, mouse; 404-86-4/Capsaicin; EC 1.14.16.2/Tyrosine 3-Monooxygenase
Comments/Corrections

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