Interchromosomal communication coordinates an intrinsically stochastic expression decision between alleles. Robert J Johnston, Claude Desplan. Biology, New York University, New York, NY.

   Stochastic cell fate specification is critical for several patterning events in nervous system development. Though morphologically uniform, the Drosophila retina is composed of two randomly distributed types of ommatidia (unit eyes) defined by expression of light-detecting Rhodopsins. Stochastic expression of the PAS-bHLH transcription factor Spineless determines the random mosaic pattern. We have found that expression of Spineless is controlled by a two step process. First, each allele of the spineless gene randomly makes an intrinsic, On/Off expression decision governed by global activation coupled with stochastic repression. When the expression decisions disagree (one allele On and one allele Off), a second step involving interchromosal communication coordinates expression state between the two alleles. This effect does not depend on chromosomal pairing or endogenous ss chromosomal position but instead requires specific DNA elements to mediate regulatory interaction. Though individual ss alleles make independent stochastic choices, interchromosomal communication ensures that they are expressed in the same subset of cells. This mechanism coupling stochastic repression with interallelic expression coordination contrasts starkly with the noisy activation mechanisms seen in bacteria and the mono-allelic, stochastic activation mechanisms observed in the mouse olfactory and human color vision systems.