In OMP-tTA TdT mice, the majority of OSNs are labeled by expression of TdTomato when fed normal chow from conception until 2 months of age (2 Mo Load). Scale bars = 200 μm in (c, d) and 20 μm in (e, f). In (e, f), the basal lamina is marked by the dotted line. (e, f) Images from the dorsal and ventral epithelial show some TdTomato labeling in OMP(−), non-neuronal cells, putatively identified as microvillar cells on the basis of morphology (marked by arrows), but OSNs remain unlabeled (marked by arrowheads). Boxed areas are shown at higher magnification in (e, f). (d) OSNs are not labeled by TdTomato in mice that were kept on doxy from conception to euthanasia. Differential expression of NQO1 (NAD(P)H:quinone oxioreductase 1) marks OSNs of dorsomedial OE. (c) A sample coronal section of the olfactory epithelium (OE) at anterior-posterior level 3 indicating the dorsal and ventral areas used for OSN quantification (boxed areas). The mice were then euthanized for tissue harvest at 2, 4, or 6 months “chase”. At these time points the mice were then switched to doxycycline-containing chow (doxy) subsequent to the switch newly maturing OSNs remain unlabeled. (a, b) In the OMP-tTA TdT mouse model, mice were maintained on normal chow from conception up to 2 months (a) or 4.5 months of age (b). Genetic recombination lifespan location in olfactory epithelium olfactory marker protein olfactory sensory neurons tetracycline responsive.Įxperimental paradigm for assaying the survival of mature OSNs in OMP-tTA TetO-Cre Rosa26-fl(stop)-TdTomato mice (referred to as OMP-tTA TdT mice) using a “pulse” (doxycycline-free)-”chase” (post doxycycline administration) design. Together, these results demonstrate spatial and temporal differences in OSN survival, highlighting it as a dynamic system that can be studied for factors affecting neuronal survival. Finally, proliferation rates anticorrelated with the spatial differences in OSN survival higher proliferation rates were observed ventrally. A spatial difference was evident: higher percentages of OSNs survived in the dorsomedial OE as compared with ventrolateral and in posterior versus anterior OE regions. Surviving OSNs were common up to 6 months chase time in both groups, but more neurons survived when loading for 4.5 months as compared with 2 months. Two loading protocols were used: conception to 2 months old and conception to 4.5 months old. We revisited the issue via the use of OMP-tTA TetO-Cre Rosa26-fl(stop)-Tdtomato (OMP-tTA TdT) mice, which allowed us to selectively label ∼95% of the OMP(+) OSN population that reach maturity by a given time and, by switching to doxycycline chow, to "chase" this preexisting OSN population. However, the estimates come with some caveats, including low labeling efficiency and a focus solely on newborn neurons. The lifespan of OSNs is still open to question, with estimates ranging from 1 month to at least 1 year. The olfactory sensory neurons (OSNs) of the olfactory epithelium (OE) exhibit a remarkable regenerative capability, which protects the population against environmental insult and enables adjustment to new odors.
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