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First published online 30 June 2004
doi: 10.1242/dev.01250
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1 Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology,
Washington University School of Medicine Pain Center, St. Louis, MO 63110,
USA
2 Department of Biochemistry and Molecular Biophysics, Columbia University, New
York, NY 10027, USA
3 Department of Biochemistry and Molecular Biology, University of Texas M.D.
Anderson Cancer Center, Houston, TX 70030, USA
Author for correspondence (e-mail:
chenz{at}morpheus.wustl.edu)
Accepted 4 May 2004
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.
Key words: Lmx1b, Dorsal horn, Migration, Differentiation, Cutaneous afferents, Mouse
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