Loss of Hoxb8 alters spinal dorsal laminae and sensory responses in mice.
Although Hox gene expression has been linked to motoneuron identity, a role of these genes in development of the spinal sensory system remained undocumented. Hoxb genes are expressed at high levels in the dorsal horn of the spinal cord. Hoxb8 null mutants manifest a striking phenotype of excessive grooming and hairless lesions on the lower back. Applying local anesthesia underneath the hairless skin suppressed excessive grooming, indicating that this behavior depends on peripheral nerve activity. Functional ablation of mouse Hoxb8 also leads to attenuated response to nociceptive and thermal stimuli. Although spinal ganglia were normal, a lower postmitotic neural count was found in the dorsalmost laminae at lumbar levels around birth, leading to a smaller dorsal horn and a correspondingly narrowed projection field of nociceptive and thermoceptive afferents. The distribution of the dorsal neuronal cell types that we assayed, including neurons expressing the itch-specific gastrin-releasing peptide receptor, was disorganized in the lumbar region of the mutant. BrdU labeling experiments and gene-expression studies at stages around the birth of these neurons suggest that loss of Hoxb8 starts impairing development of the upper laminae of the lumbar spinal cord at approximately embryonic day (E)15.5. Because none of the neuronal markers used was unexpressed in the adult dorsal horn, absence of Hoxb8 does not impair neuronal differentiation. The data therefore suggest that a lower number of neurons in the upper spinal laminae and neuronal disorganization in the dorsal horn underlie the sensory defects including the excessive grooming of the Hoxb8 mutant.
Holstege
Jan C
JC
Department of Neuroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
de Graaff
Wim
W
Hossaini
Mehdi
M
Cardona Cano
Sebastian
S
Jaarsma
Dick
D
van den Akker
Eric
E
Deschamps
Jacqueline
J
D000344:Afferent Pathways / Q000187:drug effects; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000187:drug effects / Q000473:pathology; D005727:Ganglia, Spinal / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D006579:Heterozygote; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006720:Homozygote; D006358:Hot Temperature; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D012677:Sensation / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D001616:beta-Galactosidase / Q000378:metabolism
D000779:Anesthetics, Local; D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D001616:beta-Galactosidase; D002211:Capsaicin