QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 5, 2003, 23(31):9961-9967

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (41) Citing Articles via Google Scholar Google Scholar Articles by Cheng, L. Articles by Ma, Q. Search for Related Content PubMed PubMed Citation Articles by Cheng, L. Articles by Ma, Q.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Lmx1b, Pet-1, and Nkx2.2 Coordinately Specify Serotonergic Neurotransmitter Phenotype

Leping Cheng,^1,2 * Chih-Li Chen,^1,2 * Ping Luo,^1,2 Min Tan,³ Mengsheng Qiu,³ Randy Johnson,⁴ and Qiufu Ma^1,2

¹The Dana-Farber Cancer Institute, ²Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, ³Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, Louisville, Kentucky 40292, and ⁴Program in Genes and Development, Department of Biochemistry and Molecular Biology, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

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.

Key words: Lmx1b; Pet-1; Nkx2.2; serotonergic; neurotransmitter specification; brainstem

---

Received July 18, 2003; revised August 27, 2003; accepted August 30, 2003.

This article has been cited by other articles:

				P. A. Gray Transcription factors and the genetic organization of brain stem respiratory neurons J Appl Physiol, May 1, 2008; 104(5): 1513 - 1521. [Abstract] [Full Text] [PDF]

				C. Guo, H.-Y. Qiu, Y. Huang, H. Chen, R.-Q. Yang, S.-D. Chen, R. L. Johnson, Z.-F. Chen, and Y.-Q. Ding Lmx1b is essential for Fgf8 and Wnt1 expression in the isthmic organizer during tectum and cerebellum development in mice Development, January 15, 2007; 134(2): 317 - 325. [Abstract] [Full Text] [PDF]

				F. Cote, C. Fligny, E. Bayard, J.-M. Launay, M. D. Gershon, J. Mallet, and G. Vodjdani From the Cover: Maternal serotonin is crucial for murine embryonic development PNAS, January 2, 2007; 104(1): 329 - 334. [Abstract] [Full Text] [PDF]

				Z.-Q. Zhao, M. Scott, S. Chiechio, J.-S. Wang, K. J. Renner, R. W. Gereau IV, R. L. Johnson, E. S. Deneris, and Z.-F. Chen Lmx1b Is Required for Maintenance of Central Serotonergic Neurons and Mice Lacking Central Serotonergic System Exhibit Normal Locomotor Activity J. Neurosci., December 6, 2006; 26(49): 12781 - 12788. [Abstract] [Full Text] [PDF]

				Q. Ma Transcriptional regulation of neuronal phenotype in mammals J. Physiol., September 1, 2006; 575(2): 379 - 387. [Abstract] [Full Text] [PDF]

				M. M. Scott, C. J. Wylie, J. K. Lerch, R. Murphy, K. Lobur, S. Herlitze, W. Jiang, R. A. Conlon, B. W. Strowbridge, and E. S. Deneris A genetic approach to access serotonin neurons for in vivo and in vitro studies PNAS, November 8, 2005; 102(45): 16472 - 16477. [Abstract] [Full Text] [PDF]

				F. P. O'Hara, E. Beck, L. K. Barr, L. L. Wong, D. S. Kessler, and R. D. Riddle Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer Development, July 15, 2005; 132(14): 3163 - 3173. [Abstract] [Full Text] [PDF]

				E. K. Nakakura, V. R. Sriuranpong, M. Kunnimalaiyaan, E. C. Hsiao, K. E. Schuebel, M. W. Borges, N. Jin, B. J. Collins, B. D. Nelkin, H. Chen, et al. Regulation of Neuroendocrine Differentiation in Gastrointestinal Carcinoid Tumor Cells by Notch Signaling J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4350 - 4356. [Abstract] [Full Text] [PDF]

				M. M. Scott, K. C. Krueger, and E. S. Deneris A Differentially Autoregulated Pet-1 Enhancer Region Is a Critical Target of the Transcriptional Cascade That Governs Serotonin Neuron Development J. Neurosci., March 9, 2005; 25(10): 2628 - 2636. [Abstract] [Full Text] [PDF]

				E. Mizuhara, T. Nakatani, Y. Minaki, Y. Sakamoto, and Y. Ono Corl1, a Novel Neuronal Lineage-specific Transcriptional Corepressor for the Homeodomain Transcription Factor Lbx1 J. Biol. Chem., February 4, 2005; 280(5): 3645 - 3655. [Abstract] [Full Text] [PDF]

				Y.-Q. Ding, J. Yin, A. Kania, Z.-Q. Zhao, R. L. Johnson, and Z.-F. Chen Lmx1b controls the differentiation and migration of the superficial dorsal horn neurons of the spinal cord Development, August 1, 2004; 131(15): 3693 - 3703. [Abstract] [Full Text] [PDF]

				S. E. Craven, K.-C. Lim, W. Ye, J. D. Engel, F. de Sauvage, and A. Rosenthal Gata2 specifies serotonergic neurons downstream of sonic hedgehog Development, March 1, 2004; 131(5): 1165 - 1173. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help