Ainsworth, J., Zhao, Y., Gao, K., Gravina, N.M., Goldberg, Z.H., Pinkerton, C., Rifkin, S.A., Ernst, A.M., Garcia, H.G., Perry, M.W. (2025). Cell fate ratios are encoded by transcriptional dynamics in the Drosophila retina.  Curr. Biol. 35(12): 2946--2959.e5.

FBrf0262715

Research paper

Although transcription happens in bursts, it is unclear whether variation in the rate and pattern of bursting matters during animal development. We examined whether the amount and timing of transcription influence the ratio of cell types produced during stochastic patterning of the Drosophila retina. This system is balanced between 2 outcomes: ∼70% of R7 photoreceptors (PRs) express Rhodopsin 4 (Rh4), and the rest express Rhodopsin 3 (Rh3). Cell fate depends on the cell-intrinsic binary decision to express the transcription factor spineless (Ss). Changing the ss bursting pattern by replacing the ss core promoter led to a different ratio of R7 PR types. We hypothesized that random variation in the timing of transcriptional initiation followed by autoregulation might control the outcome. Instead, we found that the decision occurs before R7 specification and before protein is made, with no feedback via Ss protein. Surprisingly, this happens in a field of progenitor cells that give rise to all retina cell types, which all initially transcribe ss. A subset stops transcribing ss over time. Those that become R7s and maintain ss transcription take the Ss-ON/Rh4 fate. Live imaging of ss transcription suggests increased time spent in off periods could decrease the probability of new transcription and therefore the Ss-ON ratio. Transiently increasing continuity of transcription produces all Ss-ON outcomes, while introducing longer gaps lowers the ratio. Targeting CBP to the ss locus increases the ratio, indicating a repressive role for chromatin state during periods when transcription is inactive. We conclude the ratio is set by the amount and dynamics of ss transcription.

PMC12208096 (PMC) (EuropePMC)