Patterning Mechanisms Underlying Notochord and Spine Segmentation in Zebrafish

The defining characteristic of the subphylum Vertebrata is the vertebral column, which is comprised of alternating vertebral bodies and intervertebral discs. In spite of being a highly conserved structure, the morphogenetic events that culminate in building the vertebral column remain poorly understood. In particular, patterning mechanisms underlying how segmentation of the spine is precisely established have not been examined at post-embryonic stages. For several years, vertebral column patterning was thought to hinge upon proper segmentation of the embryo, while the notochord served as a transient scaffold for the vertebral bodies and intervertebral discs. Using genetic, live-imaging, and quantitative approaches, this work illustrates that the notochord sheath in zebrafish, provides a template for osteoblast recruitment and vertebral bone formation in the developing spine. Furthermore, we show that notochord segmentation is influenced by the adjacent muscle segments and connective tissue, which may provide mechanical patterning cues. Insights from this work will better inform how adolescent idiopathic scoliosis and congenital scoliosis arise.