Proliferative and Transcriptional Identity of Distinct Classes of Neural Precursors in the Mammalian Olfactory Epithelium

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Proliferative and Transcriptional Identity of Distinct Classes of Neural Precursors in the Mammalian Olfactory Epithelium

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dc.contributor.author Tucker, Eric S.
dc.contributor.author Lehtinen, Maria Kristiina
dc.contributor.author Maynard, Tom
dc.contributor.author Zirlinger, Mariela
dc.contributor.author Dulac, Catherine
dc.contributor.author Rawson, Nancy
dc.contributor.author Pevny, Larysa
dc.contributor.author LaMantia, Anthony-Samuel
dc.date.accessioned 2012-11-12T21:19:56Z
dc.date.issued 2010
dc.identifier.citation Tucker, Eric S., Maria Kristiina Lehtinen, Tom Maynard, Mariela Zirlinger, Catherine Dulac, Nancy Rawson, Larysa Pevny, and Anthony-Samuel LaMantia. 2010. Proliferative and transcriptional identity of distinct classes of neural precursors in the mammalian olfactory epithelium. Development 137(15): 2471-2481. en_US
dc.identifier.issn 0950-1991 en_US
dc.identifier.issn 1477-9129 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:9888895
dc.description.abstract Neural precursors in the developing olfactory epithelium (OE) give rise to three major neuronal classes – olfactory receptor (ORNs), vomeronasal (VRNs) and gonadotropin releasing hormone (GnRH) neurons. Nevertheless, the molecular and proliferative identities of these precursors are largely unknown. We characterized two precursor classes in the olfactory epithelium (OE) shortly after it becomes a distinct tissue at midgestation in the mouse: slowly dividing self-renewing precursors that express Meis1/2 at high levels, and rapidly dividing neurogenic precursors that express high levels of Sox2 and Ascl1. Precursors expressing high levels of Meis genes primarily reside in the lateral OE, whereas precursors expressing high levels of Sox2 and Ascl1 primarily reside in the medial OE. Fgf8 maintains these expression signatures and proliferative identities. Using electroporation in the wild-type embryonic OE in vitro as well as Fgf8, Sox2 and Ascl1 mutant mice in vivo, we found that Sox2 dose and Meis1 – independent of Pbx co-factors – regulate Ascl1 expression and the transition from lateral to medial precursor state. Thus, we have identified proliferative characteristics and a dose-dependent transcriptional network that define distinct OE precursors: medial precursors that are most probably transit amplifying neurogenic progenitors for ORNs, VRNs and GnRH neurons, and lateral precursors that include multi-potent self-renewing OE neural stem cells. en_US
dc.description.sponsorship Molecular and Cellular Biology en_US
dc.language.iso en_US en_US
dc.publisher Company of Biologists en_US
dc.relation.isversionof doi:10.1242/dev.049718 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pubmed/20573694 en_US
dash.license OAP
dc.subject transcriptional network en_US
dc.subject precursor specification en_US
dc.subject peripheral olfactory system en_US
dc.subject mouse en_US
dc.title Proliferative and Transcriptional Identity of Distinct Classes of Neural Precursors in the Mammalian Olfactory Epithelium en_US
dc.type Journal Article en_US
dc.description.version Author's Original en_US
dc.relation.journal Development en_US
dash.depositing.author Dulac, Catherine
dc.date.available 2012-11-12T21:19:56Z

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  • FAS Scholarly Articles [7495]
    Peer reviewed scholarly articles from the Faculty of Arts and Sciences of Harvard University

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