The specification and generation of neurons in the ventral spinal cord

The central nervous system (CNS) of vertebrates is comprised of a diverse array of neuronal cell types located in specific regions and positions that are interconnected in circuits that form the core functional units of the structure. The correct establishment of these complex connections during development requires that cells with specific identities be generated at the proper times and positions. Moreover, as most of the major neural cell classes that populate the adult CNS, excluding the cerebellum, are generated over a relatively brief period during embryogenesis, it is necessary that the process be carried out with great precision from the outset. This involves orchestrating numerous cellular behaviors including cell division, subtype specification, migration, neurite outgrowth, and synapse formation. The degree to which each of these processes contributes to the formation of the final structure differs among CNS regions (forebrain, midbrain, hindbrain, and spinal cord). For example, the number of neurons generated during neurogenesis in the forebrain or cerebellum (postnatally) far exceeds the number in the most caudal division of the CNS, the spinal cord, and each subdivision contains distinct cell subtypes dedicated to region-specific functions. Thus, there are significant regional differences in cell division, cell cycle exit, and migration (Kelly et al., 2009). Despite these differences, many or most of the core mechanisms involved in neurogenesis are conserved throughout the CNS. Among the major CNS subdivisions, the spinal cord is unique in that it extends along the majority of the body axis in vertebrates and thus contains the longest nerve tracts. However, despite this, the spinal cord has the simplest general structure, and its basic functions are carried out by a parsimonious number of neurons organized into well-mapped nuclei. In addition, the discrete location of the spinal cord in the body provides greater experimental accessibility compared to the brain. Because of these features, the spinal cord has long served as an excellent model system for experimental investigation of CNS development for over a century (Yu et al., 2013).