Early neurogenesis in the Drosophila embryo: what is the role of lateral inhibition by Notch?

Notch-mediated lateral inhibition is a conserved patterning process that controls binary cell fate decisions. Prevailing models posit that lateral inhibition amplifies stochastic fluctuations of Notch or pre-existing spatial fate biases to single-out cells from fields of initially equipotent cells. Using quantitative live imaging of endogenous proneural gene transcription, we have revisited the temporal dynamics of neuroblast (NB) specification in the Drosophila embryonic neuroectoderm. Cells that will adopt the medial S1 NBs during germ band extension (GBE) were found to occupy a biased position along the DV axis prior to GBE. This early spatial bias in proneural gene expression predicted NB fate, indicating that NB specification is indeed pre-patterned by positional cues. Proneural genes were required for the timely onset of apical constriction but were dispensable for NB delamination, suggesting that positional cues may act in parallel to proneural genes to select individual delaminating cells in a correct stereotyped pattern. Finally, we found that the Notch effector Enhancer of split m8 factor [E(spl)m8] was not detected until after NBs begin to apically constrict, indicating that Notch does not act to single-out NBs in the early embryo. These findings challenge the current model of NB specification and led us to propose that Notch acts after the onset of NB delamination to stabilize and reinforce an initial fate difference that results from an early proneural bias established prior to GBE.