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.
Xu
Yi
Y
Dana-Farber Cancer Institute and Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Lopes
Claudia
C
Qian
Ying
Y
Liu
Ying
Y
Cheng
Leping
L
Goulding
Martyn
M
Turner
Eric E
EE
Lima
Deolinda
D
Ma
Qiufu
Q
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002766:Cholecystokinin / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D015287:Neurokinin B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000378:metabolism; D010146:Pain / Q000378:metabolism / Q000503:physiopathology*; D013004:Somatostatin / Q000378:metabolism; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism; D050819:Transcription Factor Brn-3A / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D009479:Neuropeptides; D051762:PAX2 Transcription Factor; C494189:Pou4f1 protein, mouse; D050819:Transcription Factor Brn-3A; D013373:Substance P; D013004:Somatostatin; D015287:Neurokinin B; D002766:Cholecystokinin