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dc.contributor.advisorMa, Qiufu
dc.contributor.authorLou, Shan
dc.date.accessioned2013-10-08T20:35:12Z
dash.embargo.terms2015-06-07en_US
dash.embargo.terms2015-06-07
dc.date.issued2013-10-08
dc.date.submitted2013
dc.identifier.citationLou, Shan. 2013. DEVELOPMENT AND FUNCTIONS OF C-LOW-THRESHOLD MECHANORECEPTORS. Doctoral dissertation, Harvard University.en_US
dc.identifier.otherhttp://dissertations.umi.com/gsas.harvard:10769en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11156790
dc.description.abstractSomatosensory neurons are essential for detecting diverse environmental stimuli, thus critical for survival of mammals. In order to achieve sensory modality specificity, many somatosensory subtypes emerge with various receptor and ion channel expression, as well as terminal morphologies. How the somatosensory system achieves such a high variety of neuronal subtypes is unknown. In this thesis, I used a newly discovered subtype, VGLUT3-expressing unmyelinated low-threshold mechanoreceptors (C-LTMRs), as a model to try to answer this question. C-LTMRs have been proposed to play a role in pleasant touch in humans or pain in mice. Previously, our lab has identified the Runt domain transcriptional factor Runx1 to be pivotal for the development of a cohort of sensory neurons such as pain related nociceptors, thermal receptors, as well as itch related pruriceptors. Here I found that Runx1 is also required to establish all known features associated with C-LTMRs. In search of the mechanism of how Runx1 controls C-LTMR development, I found that the zinc finger protein Zfp521 is predominantly expressed in C-LTMRs and its expression is Runx1 dependent. By generating and analyzing Zfp521 conditional knock out animals, I found Zfp521 is required for part of C-LTMR molecular identities and nerve terminal morphologies. Our studies suggest that Runx1 acts through Zfp521-dependent and Zfp521-independent pathways to specify C-LTMR identities. To study C-LTMR functions, we performed a series of behavioral analysis and found the loss of VGLUT3 and mechanosensitivities in C-LTMRs does not markedly affect acute or chronic mechanical pain measured from the hind paws, which argues against the proposed role of VGLUT3 in C-LTMRs in mediating mechanical pain in mice. In the future, we will continue to use our mutant mice to study physiological functions of C-LTMRs.en_US
dc.language.isoen_USen_US
dash.licenseLAA
dc.subjectNeurosciencesen_US
dc.subjectDevelopmental biologyen_US
dc.subjectGeneticsen_US
dc.subjectMechanoreceptoren_US
dc.subjectPiezo2en_US
dc.subjectRunx1en_US
dc.subjectSomatosensoryen_US
dc.subjectVGLUT3en_US
dc.subjectZfp521en_US
dc.titleDEVELOPMENT AND FUNCTIONS OF C-LOW-THRESHOLD MECHANORECEPTORSen_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorLou, Shan
dc.date.available2015-06-08T07:30:32Z
thesis.degree.date2013en_US
thesis.degree.disciplineBiology: Medical Sciences, Division ofen_US
thesis.degree.grantorHarvard Universityen_US
thesis.degree.leveldoctoralen_US
thesis.degree.namePh.D.en_US
dc.contributor.committeeMemberSegal, Rosalinden_US
dc.contributor.committeeMemberDong, Xinzhongen_US
dc.contributor.committeeMemberGu, Chenghuaen_US
dc.contributor.committeeMemberBean, Bruceen_US
dc.contributor.committeeMemberMacklis, Jefferyen_US
dc.contributor.committeeMemberWoolf, Clifforden_US
dash.contributor.affiliatedLou, Shan


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