Development and regenerative capacity of descending supraspinal pathways in tetrapods: a comparative approach

Throughout tetrapods a basic pattern in the organization of descending supraspinal pathways is present. The most notable difference between nonmammalian tetrapods and mammals is the apparent absence of somatomotor cortical areas giving rise to long descending projections to the spinal cord. The phylogenetic constancy of descending supraspinal pathways, at least of those arising in the brain stem, probably implies a comparable pattern of development, presumably a developmental sequence in the formation of these central motor pathways. For studies on the development of motor systems, anurans such as the clawed toad, Xenopus laevis, chicken embryos, and opossums are very attractive animals. Moreover, in these species as well as in rodents in vitro approaches can be used. In the present survey, current knowledge on the neurogenesis, axonal outgrowth, synaptogenesis, and developmental plasticity of the central motor pathways in tetrapods including the sparse data available for man, is discussed. These data are placed in the perspective of the development of the spinal cord and, where possible, correlated with functional data. Emphasis is on the clawed toad, X. laevis, chicken embryos, and opossum and rodent data. The outgrowth of axons of descending supraspinal pathways can be regarded as the result of a series of distinct processes, which may be expressed in a coordinated program: (1) the outgrowth of axons and selection of pathways to their appropriate destination; (2) dendritic outgrowth and formation of specific dendritic morphology; (3) selection of specific targets and collateralization by axons; (4) elimination of incorrect and redundant synapses, axonal and dendritic branches, and of mismatched neurons; and (5) functional refinement of synaptic connections. Tracer and transmitter immunohistochemistry in Xenopus laevis showed that from the moment cell division stops, an axon is formed followed by dendrites which emerge from the cell body. At the beginning of the cell differentiation phase the production of the cell-specific neuroactive substances takes place. Initial outgrowth is in a specific direction for each class of neuron. It is likely that all descending supraspinal pathways arise in a similar way. In the spinal projections of each of the descending supraspinal pathways three stages can be distinguished: (1) an initial stage of outgrowth to the spinal cord, (2) a short "waiting" period after which collaterals enter the spinal gray matter, and (3) myelination of axons. An "overshoot" of spinal projections is particularly evident for the mammalian corticospinal tract. The pattern of early descending axonal tracts appears to be similar in all vertebrate groups. Early axons lay down an axonal scaffold containing guidance cues that are available to later generated growth cones. Throughout vertebrates including man, the fasciculus longitudinalis medialis (flm) is the first descending pathway to be formed. Interstitiospinal fibers "pioneer" this tract, and are joined by reticulospinal fibers. Vestibulospinal fibers (the medial vestibulospinal tract) follow much later. The lateral vestibulospinal tract takes a separate course through the brain stem. Late-arriving fiber tracts such as the rubrospinal and corticospinal tracts probably have their own mechanism of selecting the appropriate pathway. The formation of the descending supraspinal pathways occurs according to a developmental sequence. In all tetrapods studied, reticulospinal and interstitiospinal fibers reach the spinal cord first, followed by vestibulospinal fibers and, much later, by rubrospinal and, if present, corticospinal projections. A special case is presented by anurans which in fact have two motor systems, a primary, transient motor system and a secondary, definitive motor system. Reticulospinal, interstitiospinal and vestibulospinal fibers innervate the spinal cord very early in development, well before the development of the hindlimbs. Rubrospinal fibers in