The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord.
Cutaneous sensory neurons that detect noxious stimuli project to the dorsal horn of the spinal cord, while those innervating muscle stretch receptors project to the ventral horn. DRG11, a paired homeodomain transcription factor, is expressed in both the developing dorsal horn and in sensory neurons, but not in the ventral spinal cord. Mouse embryos deficient in DRG11 display abnormalities in the spatio-temporal patterning of cutaneous sensory afferent fiber projections to the dorsal, but not the ventral spinal cord, as well as defects in dorsal horn morphogenesis. These early developmental abnormalities lead, in adults, to significantly attenuated sensitivity to noxious stimuli. In contrast, locomotion and sensori-motor functions appear normal. Drg11 is thus required for the formation of spatio-temporally appropriate projections from nociceptive sensory neurons to their central targets in the dorsal horn of the spinal cord.
Chen
Z F
ZF
Division of Biology 216-76 and, Howard Hughes Medical Institute, California Institute of Technology, 91125, Pasadena, CA, USA.
Rebelo
S
S
White
F
F
Malmberg
A B
AB
Baba
H
H
Lima
D
D
Woolf
C J
CJ
Basbaum
A I
AI
Anderson
D J
DJ
D000344:Afferent Pathways / Q000196:embryology / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D019521:Body Patterning; D015342:DNA Probes; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005091:Exons; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000294:innervation*; D016297:Mutagenesis, Site-Directed; D009419:Nerve Tissue Proteins; D009475:Neurons, Afferent / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000294:innervation*; D013116:Spinal Cord / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D015342:DNA Probes; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C433766:Prrxl1 protein, mouse; D014157:Transcription Factors