In essence, the precise positioning of motor columels ensures that specific motor pools are strategically placed to receive input from functionally relevant classes of proprioceptive sensory axons. What then explains the higher-order register that exists between dorso-ventral columelar selleck position in the spinal cord and proximodistal joint and muscle position in the limb? Such matching could be a reflection of developmental strategies used to assemble sensory-motor reflex arcs. In this view, inductive signals arrayed along the proximodistal axis of the limb might act on the peripheral endings of proprioceptive sensory axons to impose neuronal

subtype identities that assign their later termination zone along the dorsoventral axis of the spinal cord. Studies of chick sensory-motor circuits have provided some support for this view, in the sense that they show that limb-derived signals are able to direct central patterns

of sensory-motor connectivity (Wenner and Frank, 1995). More generally, the emerging appreciation of Romanes’s classical findings may warrant a re-evaluation of the strategies and mechanisms used to convert neuronal identity into selective connectivity. A Sperry-like view of connectivity holds that neuronal identity can be translated directly into the selectivity of expression of neuronal surface labels and argues that these labels are the primary cues recognized by incoming axons. Current thinking on the molecular underpinnings of selective synaptic connectivity is dominated by this view, despite the still scant evidence for the workings of such synaptic recognition cues. Bortezomib Viewed with seventy year hindsight (Figure 4), Romanes’s studies of neuronal order in the spinal cord serve as a timely reminder that neuronal subtype identity is as clearly reflected in the stereotypic positioning of neuronal cell bodies

as in the diversity of surface labels. Indeed, there is emerging evidence that neuronal location is a determinant of connectivity patterns, Bumetanide beyond the immediate confines of the monosynaptic sensory-motor reflex system. Recent studies of interneuron organization in the spinal cord indicate that the local inhibitory circuits that are charged with patterning the output of flexor and extensor motor neuron subtypes actually settle in different coordinate locations in the spinal cord and that such positional distinctions have consequences for patterned sensory input (Tripodi et al., 2011). In addition, the dorsoventral and mediolateral termination positions of sensory axons in the ventral nerve cord of Drosophila are established by target-independent positioning cues that, conceptually, resemble the strategy that appears to operate in mammalian spinal cord ( Zlatic et al., 2009). Finally, neuromuscular connectivity patterns in the vertebrate limb are established by mesenchymal signals that coordinate motor axonal trajectory and muscle cleavage patterns, rather than through motor recognition of target muscle ( Lewis et al.