488-444 million years ago


The early vertebrates possessed in their heads and in a series of small arches over the notochord (the beginning of vertebrae). Although they did possess collagen II which higher vertebrates incorporate in their cartilage, the cartilage of these early vertebrates was distinct and contained proteins similar to those in invertebrates. Early vertebrates did possess vitamin D and vitamin D receptors although they lacked the bone and hair which mammals synthesize using vitamin D. Although they lacked jaws, they possessed the gill arches which would evolve into jaws.

Cartilaginous fish are the most primitive animals which produce cartilage with collagen type II (and type I). Hyaline cartilage in most vertebrates possesses collagen II as its major protein with lesser amounts of collagen types VI, IX, XI, and XII. Lampreys possess cartilaginous arches above the notochord. Although type II collagen exists in the notochord of lampreys and hagfish, it is not a major component of agnathan cartilage. The major protein in lamprey cartilage is named lamprin, that of hagfish cartilage is named myxinin. Lamprin is homologous to vertebrate elastin, insect chorion proteins, and spider silk proteins (Robson, 1999). Hagfish possess two types of cartilage, one of which is not like any other known vertebrate cartilage (and is similar to cartilage-like tissues found in invertebrates) and the second of which possesses a unique protein myxinin. The alveolar cartilage of hagfish is different from that of lampreys in the amount of intercellular matrix and characteristics of the perichondrium (Tsuneki, 1993).
Vertebrates depend on vitamin D and its receptor in order to absorb the calcium necessary for the synthesis of bone. The nuclear receptor for vitamin D, VDR, activates gene transcription after binding to vitamin D. Although its major functions in mammals include the absorption of calcium for skeletal formation and regulation of the hair cycle, vitamin D receptors are expressed in lampreys which lack both bones and hair. Lampreys may use this gene to induce P450 enzymes (Whitfield, 2003).

Although lampreys lack jaws, the early development of the first pharyngeal arch, its mesoderm, and the neural crest cells are equivalent when comparing lampreys and jawed vertebrates (gnathostomes). It appears that jaws evolved from the most anterior pair of pharyngeal arches in primitive jawless fish (Horigome, 1999).