A chemoattractant role for NT-3 in proprioceptive axon guidance.
Neurotrophin-3 (NT-3) is required for proprioceptive neuron survival. Deletion of the proapoptotic gene Bax in NT-3 knockout mice rescues these neurons and allows for examination of their axon growth in the absence of NT-3 signaling. TrkC-positive peripheral and central axons from dorsal root ganglia follow proper trajectories and arrive in close proximity to their targets but fail to innervate them. Peripherally, muscle spindles are absent and TrkC-positive axons do not enter their target muscles. Centrally, proprioceptive axons branch in ectopic regions of the spinal cord, even crossing the midline. In vitro assays reveal chemoattractant effects of NT-3 on dorsal root ganglion axons. Our results show that survival factor NT-3 acts as a short-distance axon guidance molecule for muscle sensory afferents as they approach their proper targets.
Genç
Bariş
B
Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, USA.
Ozdinler
P Hande
PH
Mendoza
April E
AE
Erzurumlu
Reha S
RS
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism*; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020933:Neurotrophin 3 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020812:Receptor, trkC / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000235:genetics
D002630:Chemotactic Factors; D020933:Neurotrophin 3; D051028:bcl-2-Associated X Protein; D020812:Receptor, trkC