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Proprioception is an essential part of motor control. The main sensory subclasses that underlie this feedback control system — muscle spindle and Golgi tendon organ afferents — have been extensively characterized at a morphological and physiological level. More recent studies are beginning to reveal the molecular foundation for distinct proprioceptor subtypes, offering new insights into their developmental ontogeny and phenotypic diversity. This review intends to highlight some of these new findings.

Proprioception, the perception of body and limb position, is mediated by proprioceptors, specialized mechanosensory neurons that convey information about the stretch and tension experienced by muscles, tendons, skin and joints. In mammals, the molecular identity of the stretch-sensitive channel that mediates proprioception is unknown. We found that the mechanically activated nonselective cation channel Piezo2 was expressed in sensory endings of proprioceptors innervating muscle spindles and Golgi tendon organs in mice. Two independent mouse lines that lack Piezo2 in proprioceptive neurons showed severely uncoordinated body movements and abnormal limb positions. Moreover, the mechanosensitivity of parvalbumin-expressing neurons that predominantly mark proprioceptors was dependent on Piezo2 expression in vitro, and the stretch-induced firing of proprioceptors in muscle-nerve recordings was markedly reduced in Piezo2-deficient mice. Together, our results indicate that Piezo2 is the major mechanotransducer of mammalian proprioceptors.

The Cip/Kip family of cyclin-dependent kinase inhibitors (CKIs) has been implicated in mediating cell cycle arrest prior to terminal differentiation. In many instances, increased expression of CKIs immediately precedes mitotic arrest. However, the mechanism that activates CKI expression in cells that are about to stop dividing has remained elusive. Here we have addressed this issue by investigating the expression pattern of dacapo, a Cip/Kip CKI in Drosophila. We show that the accumulation of dacapoRNA and protein requires Cyclin E and that increased expression of Cyclin E can induce dacapoexpression. We also show that the oscillation of the Cyclin E and Dacapo proteins are tightly coupled during ovarian endocycles. Our results argue for a mechanism where Cyclin E/Cdk activity induces Dacapo expression but only within certain windows that are permissive for dacapoexpression.