542-488 million years ago

jawless fish

Before the hagfish lineage separated from that of the vertebrates, a number of additional anatomical changes had evolved. These included a hypothalamic portal system, adrenal glands, thyroid follicles, extrinsic eye muscles, a heart composed of an atrium, ventricle, and sinus venosus, heart valves, a closed circulatory system, regulation of cardiac output, a pancreas, a gall bladder, nephrons in the urinary system, and keratins in the epidermis.

Two jawless fish are known from the Early Cambrian. Myllokumingia (depicted in the above photo) had a head and trunk, a dorsal fin, a ventral fin (that might have been paired), 5-6 gill pouches, around 25 muscle segments (myomeres), a pharynx, an intestine, a notochord, and perhaps a pericardial cavity. With such features it is similar in complexity to the most primitive fish alive today, the hagfish, but perhaps slightly more advanced (Shu, 1999).

A portal system developed in the vicinity of hypothalamus and pituitary (Hoar, Vol. 2). The pituitary secreted growth hormone (Chuzhanova, 2000), structures known as follicles formed within the thyroid tissue (Hoar, Vol. 2), B and D cells were present in the endocrine pancreas (Youson, 1999), the blood supply to the endocrine pancreas increased (Jansson, 1998), cells existed which corresponded to those of the adrenal cortex in vertebrates (Hoar, Vol. 2), and steroid hormone receptors evolved (Thornton, 2001). Enkalphin and POMC genes produce signaling molecules for the nervous and endocrine system. The duplication of the single ancestral gene preceded occurred in the ancestors of the craniates (Danielson, 1999).

Early craniates possessed different types of muscle cells including both fast and slow twitch muscles (Hardisty, p. 357). Myotomes from the head region of jawless and cartilaginous fish embryos suggest that the ancestral craniate condition included pro-otic somites whose muscles produced the muscles which move the eye. The first pro-otic somite formed the superior rectus, inferior rectus, internal rectus, and inferior oblique and was innervated by the oculomotor nerve. The second pro-otic somite formed the superior oblique and was innervated by the trochlear nerve. The third pro-otic somite produced the external rectus and was innervated by the abducens nerve (Weichert, 1970). Early craniates also developed hypobranchial musculature (Romer, p. 288).

Early craniates possessed a heart with three separate chambers: the sinus venosus, a single atrium, and a single ventricle. The sinus venosus was the site where the contraction of the heart was initiated, (which is also true of the embryonic hearts of all vertebrates) (Torrey). The heart was composed of cardiac muscle (Kardong, p. 462), and its wall could be divided into an epicardium, myocardium, and endocardium (Webster, 1974, p. 129). Three heart valves (sinoatrial, atrioventricular, and semilunar heart valves) permitted only a one-way direction of flow between heart chambers (Kardong, p. 462).

Cardiac output could be varied: catecholamines stimulated moderate increases in the contraction rate and catecholamines, ANP, and neuropeptides regulated other aspects of circulatory physiology (Forster, 1997).

Although the early craniates possessed a circulatory system which was close to being a completely closed system like that of higher vertebrates, they possessed a system of venous sinuses and plexuses which were reminiscent of the open circulatory system of many invertebrates (Hardisty, p. 242). Craniates increased the number of blood vessels which serviced skeletal muscle (Willey).
The blood vessels of early craniates included external and internal carotid arteries (with internal carotids supplying the brain), celiac, anterior mesenteric, posterior mesenteric, renal, and gonadal arteries. The number of aortic arches was reduced (Romer).
The first blood cells formed in yolk sac and are nucleated (the conserved vertebrate condition even in mammals). The enzymes used by neutrophils included alkaline phosphatase (Hine, 1990). Early craniates possessed prothrombin molecules homologous to those of vertebrates (Banfield, 1994). Early craniates modified carbonic anhydrase to increase its catalytic efficiency (Tufts, 2003).

Although primitive craniates possessed thin walled vessels of vascular plexuses which functioned as primitive lymphatic vessels, there would be no true lymphatic vessels until gnathostomes (Hardisty, 249). The early craniates possessed cells homologous to the vertebrate thymus (Romer 448). The "spleen" was represented by diffuse tissue associated with the gastrointestinal tract (Torrey, 1979).
Primitive craniates possessed a protein known as CLP (complement-like protein) which functioned in immune defenses was structurally similar to a mammalian complement protein (Hanley, 1992). Although the complement system is an important component of the adaptive immunity of higher vertebrates, its original function was one of innate immunity in primitive craniates. Primitive craniates possessed complement proteins which functioned in the lectin pathway, including C3 which functioned in opsonization (the coating of a foreign object to promote its phagocytosis; Zarkadis, 2001).
Early craniates possessed heterodimeric immunoglobulins (similar to both antibodies and T cell receptors) which were secreted into the plasma as part of the immune response (Varner, 1991).
All fish, beginning with early craniates, possessed homologs of the macrophage migration inhibitory factor (MIF) (which is similar to a number of vertebrate enzymes, including some known in nematodes (Sato, 2003a).

Extensions of the dorsal mesentery around the gastrointestinal tract formed the mesentery, mesocolon, and greater momentum (the absence of the mesentery in lampreys is a secondary loss) (Romer, p. 318-9). Early craniates possessed a pancreas although the pancreatic tissue was dispersed, similar to the vertebrate condition in which multiple units form the embryonic pancreas) (Romer, p. 393-5). The liver no longer functioned in enzyme production and food absorption as it had in primitive chordates (Romer, p. 390). Craniates developed a gall bladder to store bile (Weichert, 1970, p. 194). During the formation of the mouth, only the posterior portion of the stomodeum (the anterior embryonic invagination which unites with the digestive tube) contributed to mouth (Kardong, p. 490). There was a reduction of the number of pharyngeal pouches and cartilage surrounded the pharynx (Weichert, 1970, p. 214). Early craniate digestive systems used a number of enzymes which would also be utilized by higher vertebrates such as chitinase, trypsin, aminopeptidase, and carboxypeptidase (Stevens).

In early craniates, the archinephritic duct united a series of excretory tubules and the archinephros released waste into the cloaca (Romer, p. 404). The kidney was composed of nephrons as in higher vertebrates and these nephrons consisted of a glomerular (Bowman's) capsule and regions homologous to the neck and proximal segment I of the renal tubule (Hoar, 1969, Vol. I). The early craniates utilized anterior excretory tubules known as the pronephros; although these develop in vertebrates they are non-functional and degenerate during embryonic development (Romer, p. 405).
The craniate urinary system was capable of reabsorbing filtered glucose and secreting ions (Hoar, 1969, Vol. I, p. 99).

Sermatogonia and oogonia were originated in the embryonic yolk sac (rather than the gonads), as is typical in vertebrates (Romer, p. 421). The gonads not segmented, as in many invertebrates (Weichert, p. 280).

Keratins are a family of proteins which are best known for their structural role in forming the epidermis, hair, scales, feathers, horns, and antlers of vertebrates. Several keratin genes existed in the first craniates.