Cellular and molecular mechanisms of muscle spindle development and function.

An organism's external environment is dynamic and ever-changing. Survival depends on an animal's ability to engage with its surroundings through adaptive and purpose driven movement. Organisms that rely on such movement are endowed with an internal sensory system, known as proprioception, which enables the precise detection and awareness of the body and its limbs in space. The principal receptors that give rise to this system are known as "proprioceptors", a unique population of peripheral sensory neurons embedded within skeletal muscle and tendons, referred to as muscle spindles and Golgi tendon organs, respectively. Over the years, advancements in cellular, molecular, and electrophysiological techniques have provided fundamental insight into the signaling pathways that regulate proprioceptor development. These same approaches have also facilitated the discovery of the ionic and neuromodulator mechanisms that regulate proprioceptor activity. In more recent years, emerging evidence suggests that proprioceptive feedback may engage in non-cell autonomous regulation of other physiological systems, potentially expanding their role beyond detectors of movement and force. In this review, we will examine the cellular and molecular mechanisms that govern the development and function of muscle spindle afferents. Furthermore, we will highlight their emerging influence on neurological and musculoskeletal disease.