Runx3 is essential for the target-specific axon pathfinding of trkc-expressing dorsal root ganglion neurons.
Dorsal root ganglion (DRG) neurons project their axons to specific target layers in the gray matter of the spinal cord, according to their sensory modality (Neuron 30 (2001), 707; Cell 101 (2000), 485; Neuron 31 (2001), 59; J. Comp. Neurol. 380 (1997), 215; Sensory Neurons, Oxford Univ. Press, New York, 1992, p. 131). Expression of runt-related Runx/AML genes (Mech. Dev. 109 (2001), 413) on subtypes of DRG neurons suggests their involvement in lamina-specific afferent differentiation and maturation. Here we show that Runx3-/- mice display severe limb ataxia and abnormal posture and that most of them die shortly after birth. They show that proprioceptive afferent axons fail to reach the ventral horn and have a smaller dorsal funiculus in their spinal cords. Despite the strong resemblance of this phenotype to that of knockout mice deficient in neurotrophin-3 (NT-3) (Cell 77 (1994), 503; Nature 369 (1994), 658) and its receptor, trkC, (Nature 368 (1994), 249), which show proprioceptive afferent loss through selective neuronal cell death, Runx3-/- mice maintain normal number of TrkC/trkC positive DRG neurons throughout development. Our results suggest that Runx3 controls the target-specific axon pathfinding of trkC-expressing DRG neurons in the spinal cord.
Laboratory of Cell Regulation, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Ken-ichi
K
Inoue
Shigeru
S
Ozaki
Kosei
K
Ito
Tsutomu
T
Iseda
Saburo
S
Kawaguchi
Masaharu
M
Ogawa
Suk-Chul
SC
Bae
Namiko
N
Yamashita
Shigeyoshi
S
Itohara
Norio
N
Kudo
Yoshiaki
Y
Ito
D000818:Animals; D001259:Ataxia / Q000235:genetics; D001369:Axons / Q000502:physiology*; D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005727:Ganglia, Spinal / Q000502:physiology*; D017930:Genes, Reporter; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D011187:Posture; D020812:Receptor, trkC / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D013116:Spinal Cord / Q000002:abnormalities / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D050677:Core Binding Factor Alpha 3 Subunit; D004268:DNA-Binding Proteins; C493730:Runx3 protein, mouse; D014157:Transcription Factors; D020812:Receptor, trkC; D001616:beta-Galactosidase