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. γ-Motor neurons (γ-MNs) and α-motor neurons (α-MNs) differ in size, molecular identity, synaptic input and peripheral target. While α-MNs innervate extrafusal skeletal muscle fibers to mediate muscle contraction, γ-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 γ-MNs in the mouse spinal cord by embryonic day 17.5 and continues to molecularly distinguish γ-from α-MNs into the third postnatal week. Our data demonstrate that Wnt7a is the earliest known γ-MN marker, supporting a model of developmental divergence between α- and γ-MNs at embryonic stages. Furthermore, using Wnt7a expression as an early marker of γ-MN identity, we demonstrate a previously unknown dependence of γ-MNs on a muscle spindle-derived, GDNF-independent signal during the first postnatal week.
Neuroscience Program, Weill Cornell Medical College, New York, New York 10065, USA.
Soha
S
Ashrafi
Melanie
M
Lalancette-Hébert
Andreas
A
Friese
Markus
M
Sigrist
Silvia
S
Arber
Neil A
NA
Shneider
Julia A
JA
Kaltschmidt
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D048429:Cell Size; D002470:Cell Survival; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000502:physiology; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009047:Motor Neurons, Gamma / Q000378:metabolism*; D009470:Muscle Spindles / Q000502:physiology*; D011247:Pregnancy; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*
D015415:Biomarkers; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051153:Wnt Proteins; C490508:Wnt7a protein, mouse