JAK/STAT guarantees robust neural stem cell differentiation by shutting off biological noise

Organismal development is precisely regulated by a sequence of gene functions even in the presence of biological noise. However, it is difficult to evaluate the effect of noise in vivo , and the mechanisms by which noise is filtered during development are largely unknown. To identify the noise-canceling mechanism, we used the fly visual system, in which the timing of differentiation of neural stem cells is spatio-temporally ordered. Our mathematical model predicts that JAK/STAT signaling contributes to noise canceling to guarantee the robust progression of the differentiation wave in silico . We further demonstrate that the suppression of JAK/STAT signaling causes stochastic and ectopic neural stem cell differentiation in vivo , suggesting an evolutionarily conserved function of JAK/STAT to regulate the robustness of stem cell differentiation.