title: Pbx3 is required for normal locomotion and dorsal horn development.
abstract: The transcription cofactor Pbx3 is critical for the function of hindbrain circuits controlling respiration in mammals, but the perinatal lethality caused by constitutively null mutations has hampered investigation of other roles it may play in neural development and function. Here we report that the conditional loss of Pbx3 function in most tissues caudal to the hindbrain resulted in progressive deficits of posture, locomotion, and sensation that became apparent during adolescence. In adult mutants, the size of the dorsal horn of the spinal cord and the numbers of calbindin-, PKC-gamma, and calretinin-expressing neurons in laminae I-III were markedly reduced, but the ventral cord and peripheral nervous system appeared normal. In the embryonic dorsal horn, Pbx3 expression was restricted to a subset of glutamatergic neurons, but its absence did not affect the initial balance of excitatory and inhibitory interneuron phenotypes. By embryonic day 15 a subset of Meis(+) glutamatergic neurons assumed abnormally superficial positions and the number of calbindin(+) neurons was increased three-fold in the mutants. Loss of Pbx3 function thus leads to the incorrect specification of some glutamatergic neurons in the dorsal horn and alters the integration of peripheral sensation into the spinal circuitry regulating locomotion.
authors.affiliation: Department of Neurosciences, Rm E640, Case School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Rottkamp
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Lobur
authors.forename: Cynthia L
authors.initials: CL
authors.lastname: Wladyka
authors.forename: Amy K
authors.initials: AK
authors.lastname: Lucky
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Gorman
mesh_terms: D000818:Animals; D064032:Calbindin 2; D064026:Calbindins; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000502:physiology*; D009154:Mutation; D020671:Posterior Horn Cells / Q000196:embryology / Q000254:growth & development / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D012249:Rhombencephalon / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000378:metabolism / Q000502:physiology; D013116:Spinal Cord / Q000196:embryology / Q000254:growth & development* / Q000502:physiology
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D064026:Calbindins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D064030:S100 Calcium Binding Protein G; C090466:proto-oncogene protein Pbx3; C087857:protein kinase C gamma; D011493:Protein Kinase C