Distinct and redundant roles for zebrafish her genes during mineralization and craniofacial patterning.

The Notch pathway is a cell-cell communication system which is critical for many developmental processes, including craniofacial development. Notch receptor activation induces expression of several well-known canonical targets including those encoded by the and genes in mammals and zebrafish, respectively. The function of these genes, individually and in combination, during craniofacial development is not well understood. Here, we used zebrafish genetics to investigate and gene function during craniofacial development. We found that is required for osteoblasts to efficiently mineralize bone, while cartilage is largely unaffected. Strikingly, gene expression studies in mutants indicate that although progenitor cells differentiate into osteoblasts at the appropriate time and place, they fail to efficiently lay down mineralized matrix. This mineralization role of is likely independent of Notch activation. In contrast, also functions redundantly with downstream of Jagged1b-induced Notch activation during dorsoventral craniofacial patterning. These studies disentangle distinct and redundant gene functions during craniofacial development, including an unexpected, Notch independent, requirement during bone mineralization.