Heterogeneity of Sonic Hedgehog Response Dynamics and Fate Specification in Single Neural Progenitors

During neural tube patterning, a gradient of Sonic hedgehog (Shh) signaling specifies ventral progenitor fates. The cellular response to Shh is processed through a genetic regulatory network (GRN) to code distinct fate decisions. This process integrates Shh response level, duration and other inputs and is affected by noise in signaling and cell position. How reliably a single cell’s Shh response profile predicts its fate choice is unclear. Here we use live imaging to track neural progenitors that carry both Shh and fate reporters in zebrafish embryos. We found that there is significant heterogeneity between Shh response and fate choice in single cells. We quantitatively modeled reporter intensities to obtain single cell response levels over time and systematically determined their correlation with multiple models of cell fate specification. Our input-output analysis shows that while no single metric perfectly predicts fate choices, the maximal Shh response level correlates best overall with progenitor fate choices across the anterior-posterior axis.