FIGURE 10.6. Strategies for feedback regulation of transit-amplifying cells.

FIGURE 10.6

Strategies for feedback regulation of transit-amplifying cells. (A) Simulated return to steady state, after removal of all ORNs, of a system with negative feedback regulation on the INP cell-cycle length (i.e., division rate). Note that feedback leads to modestly improved regeneration speed (over what would occur in the absence of feedback; dashed line), but only when INP numbers are almost as high as those of ORNs. (B) Simulated return to steady state, after removal of all ORNs, of a system with negative feedback regulation of the ratio of INP proliferative vs. differentiative divisions. Note the much greater improvement in regeneration speed (over absence of feedback; dashed line) without necessitating a high INP reserve. Inset shows response at early times in greater detail. (C) Dependence of rate of regeneration on the severity of initial ORN depletion, for the case shown in (B). Notice how the rate of return to steady state after a partial (75%) ORN loss (dashed gray curve) is only slightly better than in the absence of feedback (dashed black curve). (D) Simulated regeneration experiment similar to that in (C), except that both GDF11 and activin feedback loops are included in the model. Now, regeneration following 75% ORN depletion is almost as fast as from 100% depletion (compare with [C]). (Adapted from Lander, A.D. et al. PLoS Biol., 7, el5, 2009.)

From: Chapter 10, Feedback Regulation of Neurogenesis in the Mammalian Olfactory Epithelium: New Insights from Genetics and Systems Biology

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The Neurobiology of Olfaction.
Menini A, editor.
Boca Raton (FL): CRC Press/Taylor & Francis; 2010.
Copyright © 2010 by Taylor and Francis Group, LLC.

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