Brains of Primitive Chordates 439 Brains of Primitive Chordates J C Glover, University of Oslo, Oslo, Norway although providing a more direct link to the evolu- B Fritzsch, Creighton University, Omaha, NE, USA tionary clock, is nevertheless hampered by differing ã 2009 Elsevier Ltd. All rights reserved. rates of evolution, both among species and among genes, and a still largely deficient fossil record. Until recently, it was widely accepted, both on morpholog- ical and molecular grounds, that cephalochordates Introduction and craniates were sister taxons, with urochordates Craniates (which include the sister taxa vertebrata being more distant craniate relatives and with hemi- and hyperotreti, or hagfishes) represent the most chordates being more closely related to echinoderms complex organisms in the chordate phylum, particu- (Figure 1(a)). The molecular data only weakly sup- larly with respect to the organization and function of ported a coherent chordate taxon, however, indicat- the central nervous system. How brain complexity ing that apparent morphological similarities among has arisen during evolution is one of the most chordates are imposed on deep divisions among the fascinating questions facing modern science, and it extant deuterostome taxa. Recent analysis of a sub- speaks directly to the more philosophical question stantially larger number of genes has reversed the of what makes us human. Considerable interest has positions of cephalochordates and urochordates, pro- therefore been directed toward understanding the moting the latter to the most closely related craniate genetic and developmental underpinnings of nervous relatives (Figure 1(b)). system organization in our more ‘primitive’ chordate relatives, in the search for the origins of the vertebrate Comparative Appearance of Brains, brain in a common chordate ancestor. We describe Spinal Cords, and Nerves some of the principal features of the central nervous systems of hemichordates, cephalochordates, and Primitive Craniates (Cyclostomes) urochordates – taxa of increasing genetic relatedness The jawless cyclostomes, lampreys and hagfish, con- to craniates. The central nervous systems of these stitute a basic clade of craniates that shows the major taxa show a variety of forms, from a hardly specia- features of brain organization also found in gnathos- lized basiepithelial nerve plexus (hemichordates) to a tomes (jawed vertebrates). Externally, the brain of few small ganglia with a tail nerve cord (urochor- extant cyclostomes consists of a bilaterally symmetric dates), a swimming spinal cord with a barely recog- rostral enlargement, the forebrain (telencephalon), nizable cerebral vesicle (cephalochordates), and a each side of which is composed of an olfactory bulb fully developed brain and spinal cord (craniates). It and a cerebral hemisphere (Figure 2). Each hemi- is important to emphasize that although the term sphere is connected to the single, bipartite diencepha- primitive may be construed as implying a lower lon. The diencephalon gives rise to a number of rank in evolutionary sequence, we use it strictly with neural appendages. Ventrolaterally are located the respect to extant brain complexity. Each of these paired optic nerves leading to the lateral eyes. Dor- groups has in fact existed for substantial periods of sally lies a single enlargement, the habenula, that in evolutionary time and represents highly adapted life- lampreys, but not hagfish, has an attached pineal forms in their own right. We focus here on shared organ. Ventrally is located the pituitary gland. The aspects of central nervous system structure and devel- central ventricle of the diencephalon is continuous opment that may relate to a common evolutionary with the ventricle in the midbrain, the hindbrain, origin but also indicate some of the specialized struc- and the central canal of the spinal cord, all of which tural features that bear witness to the degree of diver- are greatly reduced in hagfish. Lampreys have a gence and range of derived characters that have arisen dorsal central opening in the midbrain that is covered in the several hundred million years since these by a choroid plexus, a uniquely derived feature of groups split from that origin. lampreys not shared by other craniates. Lampreys, like gnathostomes, have an oculomotor nerve leaving Phylogenetic Relationships the midbrain ventrally and a trochlear nerve exiting lateral to the cerebellum, neither of which do hagfish Originally constructed solely through comparative possess. Caudal to the small cerebellum in lampreys is analysis of morphological traits, phylogenetic trees the rhombencephalon (hindbrain) with a large cho- are being increasingly tested and revised on the roid plexus covering the IVth ventricle. A small ven- basis of gene sequence comparisons. Such analysis, tricle is also found in hagfish, but there is no trace of a 440 Brains of Primitive Chordates Hemichordates Stolidobranch Phlebobranch ascidians Thaliaceans Larvaceans ascidians Echinoderms Cephalochordates Vertebrates Urochordates Chordates a Strongylocentrotus Echinodermata Branchiostoma Cephalochordata Oikopleura Diplosoma Ciona savignyi Tunicata Ciona intestinalis Petromyzon Eptatretus Tetraodon Danio Vertebrata Olfactores Homo Gallus Xenopus Ambystoma b Figure 1 (a) Conventional scheme of phylogenetic relationships among chordates and related taxa. (b) A revised scheme based on more recent gene sequence analysis. Adapted from original image by Dr. Billie Swalla, University of Washington. choroid plexus and the presence of a cerebellum has branchial arch-derived muscle. To emphasize differ- been questioned. ences between gnathostomes and cyclostomes, the Lampreys have all the hindbrain nerves found in hagfish hindbrain, while recognizable as such, is unu- gnathostomes (trigeminal, abducens, facial, otic or sually shaped, which relates to differences in its inter- stato-acoustic, glossopharyngeus, and vagus), with nal organization. The organization of cranial nerves in the possible exception of the hypoglossal nerve. The hagfish, other than the apparent absence of the entire relative positions and fiber compositions of these extraocular muscle-related nerves, shows a number of nerves are very similar but not identical in cyclostomes deviations from gnathostome vertebrates. Hagfish and gnathostomes. For example, the abducens nerve have three completely segregated parts of the trigemi- root is almost integrated into the trigeminal nerve root nal nerve, two otic (stato-acoustic) nerves, no recog- in lampreys, whereas it is always a separate ventral nizable vagal ganglion, and a facial nerve that exits nerve root at a more caudal level in gnathostomes. dorsal to the otic nerves. Moreover, gnathostomes have three distinct motor The spinal cord in craniates is a continuous exten- neuron populations in the brain stem, each innervat- sion of the neural tissue of the hindbrain. Adult ing a different type of peripheral target: the somatic cyclostomes have unusually shaped spinal cords that motor neurons that innervate somitomere-derived are dorsolaterally flattened. Lampreys, like gnathos- musculature, the branchial motor neurons that inner- tomes, have separate dorsal and ventral roots, but vate branchial arch-derived musculature, and the visc- unlike in gnathostomes, these do not converge to eral motor neurons that innervate neural crest-derived form mixed spinal nerves and are asymmetrically parasympathetic ganglia of the head and body. In con- distributed between the left and right side. A similar trast, cyclostomes as a group lack the somatic motor but more pronounced asymmetry of spinal nerves is neurons of the hypoglossal nucleus and have no vis- exhibited by cephalochordates and has been sug- ceral motor neurons since no cranial parasympathetic gested to be primitive for chordates because an asym- ganglia are known to exist. However, the hindbrain metric pattern is also found in hagfish and some of lampreys contains so-called branchiomotor neu- gnathostomes. In hagfish, as in gnathostomes, the rons, the axons of which exit dorsally and innervate dorsal and ventral nerve roots converge, except in Brains of Primitive Chordates 441 Saccoglossus cambrensis coll. n. c. II fn. d. conc. prob. III Iv I ant.np. post .np. v d. cord 0.5 mm cil. org. p. n. ring a. n. ring v. cord Branchiostoma floridae m4 m3 m2 m1 n6 Joseph vcav n5 n4 n3 Joseph KÖlliker's pit Rohde n2 Rf Pigment cells n1 Infundibular organ Hatschek’s pit Ciona intestinalis Visceral Sensory ganglion Ocellus vesicle Nerve cord Otolith Gut Pharynx Chorda Oikopleura dioica ncg Cerebral ganglion bn3 s cf bn1 Caudal bn2 ganglion cr vso Notochord 60 µm Myxine glutinosa Diencephalon Telencephalon Medulla Tectum Spinal cord Figure 2 Continued 442 Brains of Primitive Chordates the tail region. It is believed that convergent dorsal craniates, as well as sensory neurons in dorsal root and ventral roots is a derived feature of gnathostomes ganglia. Dorsal root ganglia and proximal cranial gang- and that the superficial similarity of this feature in lia are derived from migratoryneuralcrestincraniates; hagfish is independently derived. The fiber composi- in cyclostomes, spinal dorsal root ganglia are gener- tion of spinal nerves is highly variable among cyclos- ated by neural crest, whereas cranial ganglia derive tomes and fits neither the cephalochordate nor the from placodes. In contrast to their craniate counter- basal gnathostome composition. Consequently, their parts, the dorsal root ganglion cells