Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons
文献类型：期刊论文
| 作者 | Guo, Chao ; Qiu, Hai-Yan ; Shi, Ming ; Huang, Ying ; Johnson, Randy L. ; Rubinstein, Marcelo ; Chen, Sheng-Di ; Ding, Yu-Qiang |
| 刊名 | JOURNAL OF NEUROSCIENCE
 |
| 出版日期 | 2008 |
| 卷号 | 28期号:52页码:14097-14106 |
| 关键词 | Lmx1b development midbrain dopaminergic neurons isthmic organizer substantia nigra transcription factor NAIL-PATELLA SYNDROME TYROSINE-HYDROXYLASE SEROTONERGIC NEURONS HINDBRAIN ORGANIZER SUBSTANTIA-NIGRA VENTRAL MIDBRAIN PROGENITOR CELLS ENGRAILED GENES VERTEBRATE CNS NEURAL PLATE |
| ISSN号 | 0270-6474 |
| 通讯作者 | Ding, YQ (reprint author), Chinese Acad Sci, Inst Neurosci, Key Lab Neurobiol, Shanghai 200031, Peoples R China,dingyq@ion.ac.cn |
| 英文摘要 | The LIM homeodomain transcription factor Lmx1b has been suggested to be required for the differentiation of midbrain dopaminergic (mDA) neurons. However, whether the loss of mDA neurons in Lmx1b(-/-) mice is due to its intrinsic role in the mDA lineage or to a consequence of the malformations caused by the earlier mid/hindbrain patterning defects remains to be clarified. We report here that Lmx1b expression in mDA neurons is dispensable for their differentiation and maintenance, and the loss of mDA neurons in Lmx1b(-/-) mice is due to the disruption of inductive activity of the isthmic organizer (IsO) in the absence of Lmx1b at the mid/hindbrain boundary (MHB). We found that mDA neurons revealed by tyrosine hydroxylase (TH), Pitx3, Nurr1, and dopamine transporter were indistinguishable from wild-type controls during embryonic development as well as in adulthood in TH-Cre;Lmx1b(flox/-) and Dat(Cre/+);Lmx1b(flox/-) mice, in which Lmx1b was selectively deleted in differentiating mDA neurons. In addition, mDA neurons were recovered in Lmx1b(-/-) mice, when IsO activity was restored by Wnt1-Lmx1b transgene at MHB. The restored IsO activity was evidenced by apparently normal tectum and cerebellum and recurrence of expression of Fgf8 and Wnt1 at MHB in Wnt1(Lmx1b);Lmx1b(-/-). Furthermore, when Lmx1b was deleted in the whole brain after the formation of IsO by Nestin-Cre, mDA neurons were normal, whereas serotonergic neurons displayed defective development phenocopying what observed in Lmx1b(-/-) mice. Thus, our results indicate that the inductive activity of IsO is essential, but Lmx1b expression in mDA neurons is dispensable for their differentiation and maintenance. |
| 学科主题 | Neurosciences & Neurology |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China[30721004, 30525014, 30628016, 30570637]; Ministry of Science and Technology of China[2006CB806601, 2006CB943903, 2006CB500706]; Wong Education Foundation (Hong Kong); China Postdoctoral Science Foundation[20070420678]; Chinese Academy of Sciences[KSCX2-YW-R100, KSCX2-YW-R-35] |
| 语种 | 英语 |
| 公开日期 | 2012-07-23 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1689]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Guo, Chao,Qiu, Hai-Yan,Shi, Ming,et al. Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons[J]. JOURNAL OF NEUROSCIENCE,2008,28(52):14097-14106. |
| APA | Guo, Chao.,Qiu, Hai-Yan.,Shi, Ming.,Huang, Ying.,Johnson, Randy L..,...&Ding, Yu-Qiang.(2008).Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons.JOURNAL OF NEUROSCIENCE,28(52),14097-14106. |
| MLA | Guo, Chao,et al."Lmx1b-Controlled Isthmic Organizer Is Essential for Development of Midbrain Dopaminergic Neurons".JOURNAL OF NEUROSCIENCE 28.52(2008):14097-14106. |
入库方式： OAI收割
来源：上海神经科学研究所
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