 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, December 1, 1999, 19(23):10348-10356
The ETS Domain Factor Pet-1 Is an Early and Precise Marker of Central Serotonin Neurons and Interacts with a Conserved Element in Serotonergic Genes
Timothy Hendricks, Nicole Francis, Dmitry Fyodorov, and Evan S. Deneris Case Western Reserve University, Department of Neurosciences, School of Medicine, Cleveland, Ohio 44106
Serotonin (5-HT) plays a crucial neuromodulatory role in numerous physiological and behavioral functions, and dysfunction of the serotonergic system has been implicated in several psychiatric disorders. Despite the widespread importance of the central serotonergic neurotransmitter system, little is known about the molecular mechanisms controlling the development of 5-HT neurons. We previously identified an ETS domain transcription factor, Pet-1, that is expressed in a small number of tissues, including the brain. Here, we show that expression of Pet-1 RNA in the brain is restricted to, and marks, the entire rostrocaudal extent of rat serotonergic hindbrain raphe nuclei. Remarkably, Pet-1 RNA colocalizes with tryptophan hydroxylase-positive neurons in raphe nuclei but not with their nonserotonergic neuron or non-neuronal neighbors. Pet-1 RNA is limited to two domains in the developing hindbrain, which precedes the appearance of 5-HT in each domain by approximately a half day. Conserved Pet-1 binding sites are present in or near the promoter regions of the human and mouse 5-HT1a receptor, serotonin transporter, tryptophan hydroxylase, and aromatic L-amino acid decarboxylase genes whose expression is characteristic of the serotonergic neuron phenotype. These sites are capable of supporting transcriptional activation through interactions with the Pet-1 ETS domain and can function as enhancers. Together, our findings establish Pet-1 as an early and precise marker of 5-HT neurons and suggest that it functions specifically in the differentiation and maintenance of these neurons.
Key words: serotonin; ETS factor; raphe nuclei; transcription; binding site; neurotransmitter phenotype
Copyright © 1999 Society for Neuroscience 0270-6474/99/192310348-09$05.00/0
This article has been cited by other articles:
D. Park, O. T. Shafer, S. P. Shepherd, H. Suh, J. S. Trigg, and P. H. Taghert
The Drosophila Basic Helix-Loop-Helix Protein DIMMED Directly Activates PHM, a Gene Encoding a Neuropeptide-Amidating Enzyme
Mol. Cell. Biol., January 1, 2008; 28(1): 410 - 421.
[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]
P. N Hunt, A. K McCabe, and M. M Bosma
Midline serotonergic neurones contribute to widespread synchronized activity in embryonic mouse hindbrain
J. Physiol., August 1, 2005; 566(3): 807 - 819.
[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]
P. R. Albert and S. Lemonde
5-HT1A Receptors, Gene Repression, and Depression: Guilt by Association
Neuroscientist, December 1, 2004; 10(6): 575 - 593.
[Abstract] [PDF]
E. Puelles, A. Annino, F. Tuorto, A. Usiello, D. Acampora, T. Czerny, C. Brodski, S.-L. Ang, W. Wurst, and A. Simeone
Otx2 regulates the extent, identity and fate of neuronal progenitor domains in the ventral midbrain
Development, May 1, 2004; 131(9): 2037 - 2048.
[Abstract] [Full Text] [PDF]
L. Cheng, C.-L. Chen, P. Luo, M. Tan, M. Qiu, R. Johnson, and Q. Ma
Lmx1b, Pet-1, and Nkx2.2 Coordinately Specify Serotonergic Neurotransmitter Phenotype
J. Neurosci., November 5, 2003; 23(31): 9961 - 9967.
[Abstract] [Full Text] [PDF]
X.-M. Ou, S. Lemonde, H. Jafar-Nejad, C. D. Bown, A. Goto, A. Rogaeva, and P. R. Albert
Freud-1: A Neuronal Calcium-Regulated Repressor of the 5-HT1A Receptor Gene
J. Neurosci., August 13, 2003; 23(19): 7415 - 7425.
[Abstract] [Full Text] [PDF]
C. Brodski, D. M. V. Weisenhorn, M. Signore, I. Sillaber, M. Oesterheld, V. Broccoli, D. Acampora, A. Simeone, and W. Wurst
Location and Size of Dopaminergic and Serotonergic Cell Populations Are Controlled by the Position of the Midbrain-Hindbrain Organizer
J. Neurosci., May 15, 2003; 23(10): 4199 - 4207.
[Abstract] [Full Text] [PDF]
A. Pattyn, A. Vallstedt, J. M. Dias, O. A. Samad, R. Krumlauf, F. M. Rijli, J.-F. Brunet, and J. Ericson
Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors
Genes & Dev., March 15, 2003; 17(6): 729 - 737.
[Abstract] [Full Text] [PDF]
J. Y. Sze, S. Zhang, J. Li, and G. Ruvkun
The C. elegans POU-domain transcription factor UNC-86 regulates the tph-1 tryptophan hydroxylase gene and neurite outgrowth in specific serotonergic neurons
Development, March 10, 2003; 129(16): 3901 - 3911.
[Abstract] [Full Text] [PDF]
J. McDonough, N. Francis, T. Miller, and E. S. Deneris
Regulation of Transcription in the Neuronal Nicotinic Receptor Subunit Gene Cluster by a Neuron-selective Enhancer and ETS Domain Factors
J. Biol. Chem., September 8, 2000; 275(37): 28962 - 28970.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|