title: Increased expression of tyrosine hydroxylase and anomalous neurites in catecholaminergic neurons of ATF-2 null mice.
abstract: ATF-2/CRE-BP1 was originally identified as a cAMP-responsive element (CRE) binding protein abundant in the brain. We previously reported that phosphorylation of ATF-2 increased the expression of tyrosine hydroxylase (TH), which is the rate-limiting enzyme for catecholamine biosynthesis, directly acting on the CRE in the promoter region of the TH gene in PC12D cells (Suzuki et al. [2002] J. Biol. Chem. 277:40768-40774). To examine the role of ATF-2 on transcriptional control of the TH gene in the brain, we investigated the TH expression in ATF-2-/- mice. We found that TH expression was greatly increased in medulla oblongata and locus ceruleus of the ATF-2-deficient embryos. Ectopic expression of TH was observed in the raphe magnus nucleus, where serotonergic neural cell bodies are located. Interestingly, A10 dorsal neurons were lost in the embryos of ATF-2-/- mice. There was no difference in the TH immunoreactivity in the olfactory bulb. The data showed that alteration in TH expression by absence of ATF-2 gradually declined from caudal to rostral part of the brain. We also found anomalous neurite extension in catecholaminergic neurons of ATF-2 null mice, i.e., increased dendritic arborization and shortened axons. These data suggest that ATF-2 plays critical roles for proper expression of the TH gene and for neurite extension of catecholaminergic neurons, possibly through a repressor-like action.
authors: Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors: Masayo
authors: M
authors: Kojima
authors: Takahiro
authors: T
authors: Suzuki
authors: Toshio
authors: T
authors: Maekawa
authors: Shunsuke
authors: S
authors: Ishii
authors: Chiho
authors: C
authors: Sumi-Ichinose
authors: Takahide
authors: T
authors: Nomura
authors: Hiroshi
authors: H
authors: Ichinose
mesh_terms: D051698:Activating Transcription Factor 2 / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D008125:Locus Coeruleus / Q000378:metabolism; D008526:Medulla Oblongata / Q000378:metabolism; D008636:Mesencephalon / Q000196:embryology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009411:Nerve Endings / Q000473:pathology; D016501:Neurites / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009638:Norepinephrine / Q000378:metabolism; D011149:Pons / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D014158:Transcription, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D051698:Activating Transcription Factor 2; C497106:Atf2 protein, mouse; D002395:Catecholamines; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D009638:Norepinephrine