Redundancy between components of the segmentation oscillator and the Delta/Notch pathway protects the anterior somites of zebrafish from genetic perturbation

We studied the role of cyclic HER genes, her1 and her7, in segmentation and oscillator function by inhibiting their translation with morpholinos and measuring somite formation, segment polarity, and the wave-like domains of cyclic gene expression. Loss of her1 or her7 function produces distinct defects in somitogenesis, segment polarity, and cyclic expression. Combining the effect of her1 and her7 loss causes more severe defects, including a complete absence of cyclic expression domains, suggesting that her7 and her1 are a central component of the segmentation oscillator. Muscle and bone precursors are nevertheless specified, and erratically positioned epithelial furrows form, indicating that the role of the cyclic expression domains is to position the segmental boundaries, most likely through control of segment polarity. We next studied the interaction of the oscillator with the Delta/Notch pathway by inhibiting HER translation in the deltaD/after eight, notch1a/deadly seven, and beamter mutants. Alone, these mutants show posterior segmentation defects, as does the her7 morpholinoinduced loss of function, whereas her1 loss gives isolated, mild segmental defects along the axis. Combining her7 or her1 loss with any of the mutants, or with each other, results in additional defects in the anterior paraxial mesoderm indicating that HER genes and the Delta/Notch pathway have redundant functions in anterior somitogenesis. These results, while not ruling out the existence of anterior or posterior-specific mechanisms, show that redundancy is responsible for the apparent independence of anterior and posterior somitogenesis.