Core Concepts
Fate symmetry breaking during lateral inhibition occurs at low levels of the proneural factor Scute, and cell-to-cell variations in Scute levels promote rapid fate divergence.
Abstract
The authors used live imaging and quantitative analysis to study the dynamics of the proneural factor Scute (Sc) during lateral inhibition in the developing Drosophila pupal abdomen. They found that:
Fate symmetry breaking, where cells adopt distinct fates, occurred at low levels of Sc expression, without a prolonged phase of mutual inhibition.
Cell-to-cell variations in Sc levels increased prior to fate symmetry breaking and positively correlated with the rate of fate divergence. Experimentally increasing Sc heterogeneity led to faster fate decisions.
Notch activity was minimal around the time of fate symmetry breaking, suggesting that Notch-mediated lateral inhibition acts rapidly at low proneural levels to generate the salt-and-pepper pattern of sensory organ precursor (SOP) cells.
In a small fraction of cases (~10%), pairs of neighboring cells adopted the SOP fate, but these defects were corrected through subsequent cell rearrangements.
Overall, the study provides insights into the spatial and temporal dynamics of lateral inhibition, showing that initial differences in proneural gene expression are amplified to generate stable cell fates, and that cell-to-cell heterogeneity plays a key role in promoting rapid fate divergence.
Stats
The mean number of apical neighbors for SOPs was 5.8 ± 1.1 (n=35).
The half-life of the destabilized GFP (deGFP) reporter used to monitor Notch activity was ~2 hours.
Quotes
"Fate symmetry breaking occurred at low Sc levels and that fate divergence was not preceded by a prolonged phase of low or intermediate level of Sc accumulation."
"Cell-to-cell variations in Sc levels promoted fate divergence, thereby providing experimental support for the intercellular negative feedback loop model."
"Lateral inhibition appeared to act early and fast, at low levels of proneural and Notch activities, in this tissue."