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Tlx1 and Tlx3 coordinate specification of dorsal horn pain-modulatory peptidergic neurons.

The dorsal spinal cord synthesizes a variety of neuropeptides that modulate the transmission of nociceptive sensory information. Here, we used genetic fate mapping to show that Tlx3(+) spinal cord neurons and their derivatives represent a heterogeneous population of neurons, marked by partially overlapping expression of a set of neuropeptide genes, including those encoding the anti-opioid peptide cholecystokinin, pronociceptive Substance P (SP), Neurokinin B, and a late wave of somatostatin. Mutations of Tlx3 and Tlx1 result in a loss of expression of these peptide genes. Brn3a, a homeobox transcription factor, the expression of which is partly dependent on Tlx3, is required specifically for the early wave of SP expression. These studies suggest that Tlx1 and Tlx3 operate high in the regulatory hierarchy that coordinates specification of dorsal horn pain-modulatory peptidergic neurons.

Pubmed ID: 18400903

Authors

  • Xu Y
  • Lopes C
  • Qian Y
  • Liu Y
  • Cheng L
  • Goulding M
  • Turner EE
  • Lima D
  • Ma Q

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

April 9, 2008

Associated Grants

  • Agency: NINDS NIH HHS, Id: P01 NS047572
  • Agency: NINDS NIH HHS, Id: P01 NS047572-01A10003
  • Agency: NINDS NIH HHS, Id: P01 NS047572-020003
  • Agency: NINDS NIH HHS, Id: P01 NS047572-030003
  • Agency: NINDS NIH HHS, Id: P01 NS047572-040003
  • Agency: NINDS NIH HHS, Id: P01 NS047572-050003
  • Agency: NINDS NIH HHS, Id: P01NS047572
  • Agency: NINDS NIH HHS, Id: R01 NS047710
  • Agency: NINDS NIH HHS, Id: R01 NS047710-01
  • Agency: NINDS NIH HHS, Id: R01 NS047710-02
  • Agency: NINDS NIH HHS, Id: R01 NS047710-03
  • Agency: NINDS NIH HHS, Id: R01 NS047710-04
  • Agency: NINDS NIH HHS, Id: R01 NS047710-05
  • Agency: NINDS NIH HHS, Id: R01NS47710

Mesh Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Cholecystokinin
  • Embryo, Mammalian
  • Gene Expression Regulation
  • Homeodomain Proteins
  • Mice
  • Mice, Transgenic
  • Mutation
  • Neurokinin B
  • Neurons
  • Neuropeptides
  • PAX2 Transcription Factor
  • Pain
  • Somatostatin
  • Spinal Cord
  • Substance P
  • Transcription Factor Brn-3A
  • Transcription, Genetic