Stochastic neuronal cell fate choices

Abstract

Though many neuronal cell fate decisions result in reproducible outcomes, stochastic choices often lead to spatial randomization of cell subtypes. This is often the case in sensory systems where expression of a specific sensory receptor gene is selected randomly from a set of possible outcomes. Here, we describe recent findings elucidating the mechanisms controlling color photoreceptor subtypes in flies and olfactory receptor subtypes in worms and mice. Although well-known biological concepts such as lateral signaling and promoter selection play roles in these cases, fundamental questions concerning these choice mechanisms remain.

Fig. 1. Olfactory subtype selection in mice

(a) “Selector” machinery activates expression of a single OR gene. (b) “Selector” machinery activates the H-region enhancer which selects an OR gene from a proximal cluster for expression. (c) OR protein coding region is required for repression of other OR genes. (d) OR protein coding regions contain cis-regulatory elements that mediate repression despite the presence of a heterologous promoter.

Fig. 2. Color photoreceptor subtype selection in flies

(a) The random mosaic of color photoreceptor expression. (b) Spineless controls the pale vs. yellow subtype choice.

Fig. 3. Olfactory subtype selection in worms

(a) Random expression of str-2 in AWC neurons. AWC^on fate is determined by str-2 expression (in red). srsx-3 is a genetic marker for AWC^off fate (in green). Asterisks(*) indicate expression in non-AWC cells. (b) AWCL is biased to NSY-4 activity whereas AWCR is biased to NSY-5 activity. Lateral inhibition via a Ca²⁺ mediated mechanism promotes AWC^on fate (high NSY-4 and NSY-5 activity) in a neuron while activating AWC^off fate (low NSY-4 and NSY-5 activity) in the other neuron.