Molecular and developmental insights into proprioceptive identity in the mesencephalic trigeminal nucleus neurons

The mesencephalic trigeminal nucleus (MTN) contains trigeminal proprioceptive neurons, a unique class of primary sensory neurons with centrally located cell bodies and a developmental origin distinct from that of peripheral ganglion-derived spinal proprioceptors. MTN neurons have long been recognized for their morphological heterogeneity, but their functions were traditionally viewed as confined to the jaw jerk reflex and oromotor control, reflecting their predominant innervation of jaw-closing muscles. Recent single-cell transcriptomic studies have provided new insight into MTN neurons by uncovering molecular determinants of proprioceptive identity, revealing discrete transcriptional programs that underlie their developmental trajectories and functional specialization. While some subsets of MTN neurons share features with Group Ia and II proprioceptors, they are distinguished by characteristic molecular signatures, including the absence of <i>Runx3</i>, differential <i>Ntrk2</i> and <i>Ntrk3</i> expression, and broader transcriptional features that are not observed in classical spinal counterparts. Accumulating evidence also supports a functional role for MTN neurons in the behavioral transition from suckling to mastication during the weaning period in mammals. In this review, we integrate anatomical, molecular, and functional perspectives to refine the proprioceptive identity of MTN neurons and highlight their implications for sensorimotor maturation and developmental disorders.