TY - JOUR T1 - <em>Lmx1b, Pet-1</em>, and <em>Nkx2.2</em> Coordinately Specify Serotonergic Neurotransmitter Phenotype JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9961 LP - 9967 DO - 10.1523/JNEUROSCI.23-31-09961.2003 VL - 23 IS - 31 AU - Leping Cheng AU - Chih-Li Chen AU - Ping Luo AU - Min Tan AU - Mengsheng Qiu AU - Randy Johnson AU - Qiufu Ma Y1 - 2003/11/05 UR - http://www.jneurosci.org/content/23/31/9961.abstract N2 - 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. ER -