Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents.
To study the role of NT3 in directing axonal projections of proprioceptive dorsal root ganglion (DRG) neurons, NT3(-/-) mice were crossed with mice carrying a targeted deletion of the proapoptotic gene Bax. In Bax(-/-)/NT3(-/-) mice, NT3-dependent neurons survived and expressed the proprioceptive neuronal marker parvalbumin. Initial extension and collateralization of proprioceptive axons into the spinal cord occurred normally, but proprioceptive axons extended only as far as the intermediate spinal cord. This projection defect is similar to the defect in mice lacking the ETS transcription factor ER81. Few if any DRG neurons from Bax(-/-)/NT3(-/-) mice expressed ER81 protein. Expression of a NT3 transgene in muscle restored DRG ER81 expression in NT3(-/-) mice. Finally, addition of NT3 to DRG explant cultures resulted in induction of ER81 protein. Our data indicate that NT3 mediates the formation of proprioceptive afferent-motor neuron connections via regulation of ER81.
Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Tushar D
TD
Patel
Ina
I
Kramer
Jan
J
Kucera
Vera
V
Niederkofler
Thomas M
TM
Jessell
Silvia
S
Arber
William D
WD
Snider
D000344:Afferent Pathways / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D005260:Female; D005333:Fetus; D005727:Ganglia, Spinal / Q000196:embryology* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009470:Muscle Spindles / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D018482:Muscle, Skeletal / Q000196:embryology / Q000254:growth & development / Q000294:innervation; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000172:deficiency* / Q000235:genetics; D011434:Proprioception / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D015398:Signal Transduction / Q000235:genetics; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics; D051028:bcl-2-Associated X Protein
C494827:Bax protein, mouse; D004268:DNA-Binding Proteins; C490641:Etv1 protein, mouse; D020933:Neurotrophin 3; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein