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| Home > Publications Database > Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling. > print |
| Home > Publications Database > Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling. > print |
| 001 | 154266 | ||
| 005 | 20230915094030.0 | ||
| 024 | 7 | _ | |a 10.3389/fcell.2020.587778 |2 doi |
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| 037 | _ | _ | |a DZNE-2021-00120 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Nouri, Parivash |b 0 |
| 245 | _ | _ | |a Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling. |
| 260 | _ | _ | |a Lausanne |c 2020 |b Frontiers Media |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 500 | _ | _ | |a ISSN 2296-634X not unique: **3 hits**. |
| 520 | _ | _ | |a The mesodiencephalic dopaminergic (mdDA) neurons, including the nigrostriatal subset that preferentially degenerates in Parkinson's Disease (PD), strongly depend on an accurately balanced Wingless-type MMTV integration site family member 1 (WNT1)/beta-catenin signaling pathway during their development. Loss of this pathway abolishes the generation of these neurons, whereas excessive WNT1/b-catenin signaling prevents their correct differentiation. The identity of the cells responding to this pathway in the developing mammalian ventral midbrain (VM) as well as the precise progression of WNT/b-catenin action in these cells are still unknown. We show that strong WNT/b-catenin signaling inhibits the differentiation of WNT/b-catenin-responding mdDA progenitors into PITX3+ and TH+ mdDA neurons by repressing the Pitx3 gene in mice. This effect is mediated by RSPO2, a WNT/b-catenin agonist, and lymphoid enhancer binding factor 1 (LEF1), an essential nuclear effector of the WNT/b-catenin pathway, via conserved LEF1/T-cell factor binding sites in the Pitx3 promoter. LEF1 expression is restricted to a caudolateral mdDA progenitor subset that preferentially responds to WNT/b-catenin signaling and gives rise to a fraction of all mdDA neurons. Our data indicate that an attenuation of WNT/b-catenin signaling in mdDA progenitors is essential for their correct differentiation into specific mdDA neuron subsets. This is an important consideration for stem cell-based regenerative therapies and in vitro models of neuropsychiatric diseases. |
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| 650 | _ | 7 | |a Parkinson’s disease |2 Other |
| 650 | _ | 7 | |a dopamine |2 Other |
| 650 | _ | 7 | |a mouse |2 Other |
| 650 | _ | 7 | |a nerve cell |2 Other |
| 650 | _ | 7 | |a regenerative therapy |2 Other |
| 700 | 1 | _ | |a Götz, Sebastian |b 1 |
| 700 | 1 | _ | |a Rauser, Benedict |b 2 |
| 700 | 1 | _ | |a Irmler, Martin |b 3 |
| 700 | 1 | _ | |a Peng, Changgeng |b 4 |
| 700 | 1 | _ | |a Trümbach, Dietrich |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Kempny, Christian |b 6 |
| 700 | 1 | _ | |a Lechermeier, Carina G |b 7 |
| 700 | 1 | _ | |a Bryniok, Agnes |b 8 |
| 700 | 1 | _ | |a Dlugos, Andrea |b 9 |
| 700 | 1 | _ | |a Euchner, Ellen |b 10 |
| 700 | 1 | _ | |a Beckers, Johannes |b 11 |
| 700 | 1 | _ | |a Brodski, Claude |b 12 |
| 700 | 1 | _ | |a Klümper, Claudia |b 13 |
| 700 | 1 | _ | |a Wurst, Wolfgang |0 P:(DE-2719)2000028 |b 14 |u dzne |
| 700 | 1 | _ | |a Prakash, Nilima |0 P:(DE-HGF)0 |b 15 |e Corresponding author |
| 773 | _ | _ | |a 10.3389/fcell.2020.587778 |g Vol. 8, p. 587778 |0 PERI:(DE-600)2737824-X |p 587778 |t Frontiers in cell and developmental biology |v 8 |y 2020 |x 2296-634X |
| 856 | 4 | _ | |u https://www.frontiersin.org/articles/10.3389/fcell.2020.587778/full |
| 856 | 4 | _ | |u https://pub.dzne.de/record/154266/files/18584.pdf |y OpenAccess |
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