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. Author manuscript; available in PMC: 2018 Mar 1.
Published in final edited form as: J Comp Neurol. 2016 Sep 27;525(4):1034–1054. doi: 10.1002/cne.24105

Figure 4.

Figure 4

Diagram illustrating the process of epitheliopoiesis in the OE during recovery from methyl bromide (MeBr) injury, which is substantially more complex than the progression observed in the normal OE (cf. Fig. 3). The cellular lineages to which basal cells give rise and the timing of their re-emergence after damage (shaded ovals in the background) are indicated. The rainbow gradient filling the GBCSTEM and GBCMPP symbolizes their active multipotency, i.e., those GBCs that generate, in aggregate, all of the epithelial cell types following epithelial injury, including HBCs. The self-renewal capacity of the GBCSTEM is indicated by the circular arrow; self renewal is strongly suggested by the persistence of neurogenesis when the contribution of HBCs has been eliminated (see Fig. 5 and text for details). Thus, some GBCs satisfy both the multipotency and self-renewal criteria for being classified as stem cells. The retention of thymidine label by some GBCs also suggests stem-like quiescence. As an example of GBC multipotency, 1 day after MeBr (darkest purple oval), the epithelium consists of HBCs and GBCs, characterized by the indicated transcription factor profiles, including the selective HBC marker p63. Some among the GBCs express Hes1, which marks the GBCs that are transitioning directly into Sus cells. Notch signaling is key to the determination of neuronal vs. nonneuronal differentiation (Herrick and Schwob, 2015). Also indicated is the dual origin of the Sus cells from GBCs and from gland/duct cells, which has been demonstrated by retroviral lineage tracing and transplantation experiments, as summarized in the text (Huard et al., 1998). GBCSTEM, stem cell-like GBC expressing Sox2 and Pax6 that is mitotically quiescent (thymidine label-retaining); GBCMPP, multipotent GBC expressing Sox2 and Pax6 and appearing first during development and regeneration; GBCTA-OSN, transit-amplifying GBC restricted to the neuronal lineage and expressing Sox2, Pax6, and Ascl1; GBCINP, GBC functioning as an immediate neuronal precursor, i.e., giving rise to a small number of OSNs, and expressing Neurog1 and NeuroD1.