Pbx3 is required for normal locomotion and dorsal horn development

Catherine Rottkamp, Katherine J. Lobur, Cynthia L. Wladyka, Amy K. Lucky, Stephen O'Gorman

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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-γ, 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.

Original languageEnglish (US)
Pages (from-to)23-39
Number of pages17
JournalDevelopmental Biology
Volume314
Issue number1
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

Keywords

  • Calbindin
  • Dorsal horn
  • GABA
  • Glutamate
  • Hox genes
  • Lamination
  • Meis
  • Movement disorder
  • Spinal cord
  • Tlx genes

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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