Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord.
The differentiation and migration of superficial dorsal horn neurons and subsequent ingrowth of cutaneous afferents are crucial events in the formation of somatosensory circuitry in the dorsal spinal cord. We report that the differentiation and migration of the superficial dorsal horn neurons are regulated by the LIM homeobox gene Lmx1b, and its downstream targets Rnx and Drg11, two transcription factors implicated in the development of dorsal horn circuitry. An analysis of Lmx1b mutants shows that Lmx1b normally acts to maintain the expression of the Ebf genes and to repress the Zic genes. Lmx1b mutants also exhibit the disruption of the cutaneous afferent ingrowth, suggesting that the dorsal horn cells might provide important cues guiding sensory axons into the dorsal spinal cord. Our results thus indicate that Lmx1b has a pivotal role in genetic cascades that control the assembly of circuitry in the superficial dorsal horn.
Ding
Yu-Qiang
YQ
Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology, Washington University School of Medicine Pain Center, St. Louis, MO 63110, USA.
Yin
Jun
J
Kania
Artur
A
Zhao
Zhong-Qiu
ZQ
Johnson
Randy L
RL
Chen
Zhou-Feng
ZF
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D060850:LIM-Homeodomain Proteins; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020671:Posterior Horn Cells / Q000166:cytology / Q000502:physiology*; D011247:Pregnancy; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; C112149:LIM homeobox transcription factor 1 beta; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; C491060:Phox2a protein, mouse; C433766:Prrxl1 protein, mouse; C487377:Tlx3 protein, mouse; D014157:Transcription Factors; C492122:Zic1 protein, mouse; C100431:Zic4 protein, mouse; D020917:Receptor, trkA