Rewiring the taste system.

Abstract

In mammals, taste buds typically contain 50-100 tightly packed taste receptor cells (TRCs) representing all five basic qualities: sweet, sour, bitter, salty and umami1,2. Notably, mature taste cells have life spans of only 5-20 days, and consequently, are constantly replenished by differentiation of taste stem cells3. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (i.e. ensuring that a labeled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, etc.), we examined how new connections are specified to retain fidelity of signal transmission. Our results show that bitter and sweet TRCs provide instructive signals to bitter and sweet target neurons via different guidance molecules (Sema3A and Sema7A)4-6. Here, we demonstrate that targeted expression of Sema3A or Sema7A in different classes of TRCs produce peripheral taste systems with miswired sweet or bitter cells. Indeed, we engineered animals whereby bitter neurons now respond to sweet tastants, sweet neurons respond to bitter, or with sweet neurons responding to sour stimuli. Together, these results uncover the basic logic of the wiring of the taste system at the periphery, and illustrate how a labeled-line sensory circuit preserves signaling integrity despite rapid and stochastic turnover of receptor cells.