Neurons (Kania, 2014; McArthur and Fetcho, 2017). As

Neurons grouped themselves with others that sharing the same function by either organized into stratified layers or forming clusters of nuclei by nucleogenesis (Pearson et al., 2014). Yet, whether an accurate topographic arrangement of neurons is prerequisite for proper muscle innervation remains largely unknown. Demireva first found that from embryonic to postnatal stages in mice, there is a broad co-expression of ?- and ?-catenin proteins in the spinal motor neurons. By genetically ablating both ?- and ?-catenin from spinal motor neurons using single or double conditional mutant Olig2::Cre line, they observed a disruption of motor column organization of median motor and preganglionic columns, and unequal divisions of lateral motor column neurons and motor pool segregation failure. Surprisingly, these perturbations of motor neurons have no influence on transcription factor expression and the neuronal projections toward their muscle target as illustrated in Figure1. Since the innervation is independent of motor neuron positioning, it questions the reason of consuming energy on the topographic arrangement of motor neurons during development (Demireva et al., 2011) as well as the necessity of neuronal migration during spinal cord circuitry development (Kania, 2014; McArthur and Fetcho, 2017). As Demireva hypothesized, the topographic map of motor neurons is a representative of non-linear framework found exclusively in the central nervous system to avoid confounding the various inputs to the output pathways (Demireva et al., 2011). It then seems reasonable to reckon this topographic organization must possess additional functions to be evolutionarily conserved. Indeed, the motor pool sorting is believed to enhance neuromuscular connections by separating neurons that share the same muscle target to ensure a coherent neuron firing (Personius et al., 2007). Furthermore, as in the canonical reflex arc, afferent sensory neurons in the spinal cord link the efferent motor neurons via interneurons in between, the misplaced motor neurons could lead to position modification in sensory and interneurons. Evidence of this was claimed in the research by Surmeli et al. which reported that motor pool positioning is crucial for the establishment of functional sensory-motor connectivity since the monosynaptic associations between motor neurons and the proprioceptors of muscle formed in a topographic manner rather than on neuronal identity base (Surneli et al., 2011; Bikoff et al., 2016). Besides, the relationship between interneuron arrangement and motor neuron target connectivity was answered in 2016 by Bikoff et al. where they demonstrated there is no predictable link between interneuron positions and the muscle targets whereas the input connectivity seems to confine the interneuron organizations.