title: p63 regulates olfactory stem cell self-renewal and differentiation.
abstract: The olfactory epithelium is a sensory neuroepithelium that supports adult neurogenesis and tissue regeneration following injury, making it an excellent model for investigating neural stem cell regulation in vivo. Previous studies have identified the horizontal basal cell (HBC) as the neural stem cell of the postnatal olfactory epithelium. However, the molecules and pathways regulating HBC self-renewal and differentiation are unknown. In the present study, we demonstrate that the transcription factor p63, a member of the p53 tumor suppressor gene family known to regulate stem cell dynamics in other epithelia, is highly enriched in HBCs. We show that p63 is required cell autonomously for olfactory stem cell renewal and further demonstrate that p63 functions to repress HBC differentiation. These results provide critical insight into the genetic regulation of the olfactory stem cell in vivo and more generally provide an entrée toward understanding the coordination of stem cell self-renewal and differentiation.
authors.affiliation: Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute & Functional Genomics Laboratory, University of California, Berkeley, CA 94720-3200, USA.
authors.forename: Russell B
authors.initials: RB
authors.lastname: Fletcher
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Prasol
authors.forename: Jose
authors.initials: J
authors.lastname: Estrada
authors.forename: Ariane
authors.initials: A
authors.lastname: Baudhuin
authors.forename: Karen
authors.initials: K
authors.lastname: Vranizan
authors.forename: Yoon Gi
authors.initials: YG
authors.lastname: Choi
authors.forename: John
authors.initials: J
authors.lastname: Ngai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009830:Olfactory Bulb / Q000166:cytology*; D009831:Olfactory Mucosa / Q000166:cytology; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics; D022661:RNA, Untranslated; D013234:Stem Cells / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D053569:Keratin-15; D053555:Keratin-5; C492053:Krt15 protein, mouse; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D011506:Proteins; D022661:RNA, Untranslated; D015534:Trans-Activators; C486419:Trp63 protein, mouse; C054562:yellow fluorescent protein, Bacteria