title: Sox2 and Pax6 Play Counteracting Roles in Regulating Neurogenesis within the Murine Olfactory Epithelium.
abstract: In the adult olfactory epithelium, the transcription factors Pax6 and Sox2 are co-expressed in sustentacular cells, horizontal basal cells (HBCs), and less-differentiated globose basal cells (GBCs)-both multipotent and transit amplifying categories-but are absent from immediate neuronal precursor GBCs and olfactory sensory neurons (OSNs). We used retroviral-vector transduction to over-express Pax6 and Sox2 individually and together during post-lesion recovery to determine how they regulate neuronal differentiation. Both Pax6 and Sox2, separately and together, can suppress the production of OSNs, as fewer clones contain neurons than with empty vector (EV), although this effect is not absolute. In this regard, Pax6 has the strongest effect when acting alone. In clones where neurons form, Pax6 reduces neuron numbers by comparison with EV, while Sox2 expands their numbers. Co-transduction with Pax6 and Sox2 produces an intermediate result. The increased production of OSNs driven by Sox2 is due to the expansion of neuronal progenitors, since proliferation and the numbers of Ascl1, Neurog1, and NeuroD1-expressing GBCs are increased. Conversely, Pax6 seems to accelerate neuronal differentiation, since Ascl1 labeling is reduced, while Neurog1- and NeuroD1-labeled GBCs are enriched. As a complement to the over-expression experiments, elimination of Sox2 in spared cells of floxed Sox2 mice, by retroviral Cre or by K5-driven CreERT2, reduces the production of OSNs and non-neuronal cells during OE regeneration. These data suggest that Pax6 and Sox2 have counteracting roles in regulating neurogenesis, in which Pax6 accelerates neuronal production, while Sox2 retards it and expands the pool of neuronal progenitors.
authors.affiliation: Graduate Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Packard
authors.affiliation: Graduate Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Lin
authors.affiliation: Graduate Program in Cellular, Molecular and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, Massachusetts, United States of America.|Department of Developmental, Molecular and Chemical Biology, Tufts University, School of Medicine, Boston, Massachusetts, United States of America.
authors.forename: James E
authors.initials: JE
authors.lastname: Schwob
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D048429:Cell Size; D002999:Clone Cells; D004848:Epithelium / Q000378:metabolism; D017353:Gene Deletion; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D000071841:PAX6 Transcription Factor / Q000378:metabolism*; D012038:Regeneration; D012190:Retroviridae / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D000071841:PAX6 Transcription Factor; C000605732:Pax6 protein, mouse; D055748:SOXB1 Transcription Factors; C527783:Sox2 protein, mouse