A unique and conserved feature of all DRG sensory neurons is the

A unique and conserved feature of all DRG sensory neurons is the establishment of two distinct axonal processes, extending from DRG cell bodies toward peripheral and central targets. Sensory neuron subtypes differ in identity of these targets, thereby channeling functionally distinct primary sensory information to dedicated spinal subcircuits for integration and processing. Group Ia proprioceptors account perhaps for the most studied DRG

sensory neuron subtype, owing to their unique IPI-145 wiring properties into monosynaptic reflex circuits directly connecting sensory feedback to motor output. Their peripheral projections target muscle spindles, sensors embedded within skeletal muscles and endowed with detecting changes in muscle contraction (Brown, 1981 and Scott, 1992). Their central projections dive deep into the spinal cord to establish direct synaptic connections with motor neurons (Brown, 1981, Burke and Glenn, 1996 and Eccles et al., 1957). The monosynaptic reflex arc is highly

suitable to understand mechanisms driving synaptic specificity programs. Direct sensory-motor connections exhibit a high degree of synaptic specificity, as assessed extensively by electrophysiological methods in several species (Eccles et al., 1957 and Mears and Frank, 1997). These studies demonstrate the existence of numerous and strong connections between homonymous Lumacaftor sensory-motor pairs projecting to the same peripheral target muscle and a lower degree of connectivity between synergistic or functionally related pairs. In contrast, synaptic connections between antagonistic or functionally

unrelated sensory-motor pairs are negligible. Transcriptional programs expressed in motor neuron column- and pool-specific patterns are tightly and causally linked to the establishment of accurate Ibrutinib motor axonal trajectories to target muscles. Combinatorial expression of Hox and Lim-homeobox transcription factors by motor neuron subpopulations at early postmitotic stages instructs axonal outgrowth to target muscles by control of downstream signaling molecules (Dalla Torre di Sanguinetto et al., 2008, Dasen et al., 2005, Jessell, 2000, Kania and Jessell, 2003 and Shirasaki and Pfaff, 2002). At later stages, target-derived cues act to control additional aspects of motor neuron differentiation in part by regulation of ETS transcription factors (Dalla Torre di Sanguinetto et al., 2008, Haase et al., 2002, Livet et al., 2002 and Vrieseling and Arber, 2006). These collective observations on peripheral targeting mechanisms raise the question of whether and how motor neuron pool-specific genetic programs are also instrumental in controlling the establishment of central connectivity, including sensory-motor specificity.

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