Wnt7A Identifies Embryonic γ-Motor Neurons and Reveals Early Postnatal Dependence of γ-Motor Neurons on a Muscle Spindle-Derived Signal

Motor pools comprise a heterogeneous population of motor neurons that innervate distinct intramuscular targets. While the organization of motor neurons into motor pools has been well described, the time course and mechanism of motor pool diversification into functionally distinct classes remains unclear. gamma-Motor neurons (gamma-MNs) and alpha-motor neurons (alpha-MNs) differ in size, molecular identity, synaptic input and peripheral target. While alpha-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, gamma-MNs innervate intrafusal fibers of the muscle spindle, and regulate sensitivity of the muscle spindle in response to stretch. In this study, we find that the secreted signaling molecule Wnt7a is selectively expressed in gamma-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish gamma-from alpha-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known gamma-MN marker, supporting a model of developmental divergence between alpha- and gamma-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of gamma-MN identity, we demonstrate a previously unknown dependence of gamma-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.