Nature Neuroscience6, 933 - 938 (2003)
Published online: 3 August 2003; | doi:10.1038/nn1104
Lmx1b is essential for the development of serotonergic neurons
Yu-Qiang Ding1, Ulrika Marklund2, Wenlin Yuan1, Jun Yin1, Lauren Wegman3, Johan Ericson2, Evan Deneris3, Randy L Johnson4
& Zhou-Feng Chen1
1
Departments of Anesthesiology, Psychiatry, Molecular Biology and Pharmacology, School of Medicine Pain Center, Washington University, St. Louis, Missouri 63110, USA.
2
Department of Cell and Molecular Biology, Karolinska Institute S-171 77 Stockholm, Sweden.
3
Department of Neuroscience, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA.
4
Department of Biochemistry and Molecular Biology, University of Texas, MD Anderson Cancer Center, Houston 77030, USA.
The specification and differentiation of serotonergic (5-HT) neurons require both extrinsic signaling molecules and intrinsic transcription factors to work in concert or in cascade. Here we identify the genetic cascades that control the specification and differentiation of 5-HT neurons in mice. A major determinant in the cascades is an LIM homeodomain-containing gene, Lmx1b, which is required for the development of all 5-HT neurons in the central nervous system. Our results suggest that, during development of 5-HT neurons, Lmx1b is a critical intermediate factor that couples Nkx2-2−mediated early specification with Pet1-mediated terminal differentiation. Moreover, our data indicate that genetic cascades controlling the caudal and rostral 5-HT neurons are distinct, despite their shared components.
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