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Publication : Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype.

First Author  Cheng L Year  2003
Journal  J Neurosci Volume  23
Issue  31 Pages  9961-7
PubMed ID  14602809 Mgi Jnum  J:86557
Mgi Id  MGI:2680758 Doi  10.1523/JNEUROSCI.23-31-09961.2003
Citation  Cheng L, et al. (2003) Lmx1b, Pet-1, and Nkx2.2 coordinately specify serotonergic neurotransmitter phenotype. J Neurosci 23(31):9961-7
abstractText  Serotonergic (5-HT) neurons in the brainstem modulate a wide range of physiological processes and behaviors. Two transcription factor genes, Pet-1 and Nkx2.2, are necessary but not sufficient to specify the 5-HT transmitter phenotype. Here we show that the Lim class homeobox gene Lmx1b is required for proper formation of the entire 5-HT system in the hindbrain, as indicated by the loss of expression of genes necessary for serotonin synthesis and transport in Lmx1b null mice. Lmx1b and Pet1 act downstream of Nkx2.2, and their expression is independently regulated at the time when 5-HT transmitter phenotype is specified. Ectopic expression of Lmx1b plus Pet-1 is able to induce formation of 5-HT cells in the most ventral spinal cord, where Nkx2.2 is normally expressed. Combined expression of all three genes, Lmx1b, Pet-1, and Nkx2.2, drives 5-HT differentiation in the dorsal spinal cord. Our studies therefore define a molecular pathway necessary and sufficient to specify the serotonergic neurotransmitter phenotype.
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