The impact of Drew Noden's work on our understanding of craniofacial musculoskeletal integration.

The classical anatomist Drew Noden spearheaded craniofacial research, laying the foundation for our modern molecular understanding of development, evolution, and disorders of the craniofacial skeleton. His work revealed the origin of cephalic musculature and the role of cranial neural crest (CNC) in early formation and patterning of the head musculoskeletal structures. Much of modern cranial tendon research advances a foundation of knowledge that Noden built using classical quail-chick transplantation experiments. This elegant avian chimeric system involves grafting of donor quail cells into host chick embryos to identify the cell types they can form and their interactions with the surrounding tissues. In this review, we will give a brief background of vertebrate head formation and the impact of CNC on the patterning, development, and evolution of the head musculoskeletal attachments. Using the zebrafish as a model system, we will discuss examples of modifications of craniofacial structures in evolution with a special focus on the role of tendon and ligaments. Lastly, we will discuss pathologies in craniofacial tendons and the importance of understanding the molecular and cellular dynamics during craniofacial tendon development in human disease.