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@ARTICLE{Nouri:154266,
author = {Nouri, Parivash and Götz, Sebastian and Rauser, Benedict
and Irmler, Martin and Peng, Changgeng and Trümbach,
Dietrich and Kempny, Christian and Lechermeier, Carina G and
Bryniok, Agnes and Dlugos, Andrea and Euchner, Ellen and
Beckers, Johannes and Brodski, Claude and Klümper, Claudia
and Wurst, Wolfgang and Prakash, Nilima},
title = {{D}ose-{D}ependent and {S}ubset-{S}pecific {R}egulation of
{M}idbrain {D}opaminergic {N}euron {D}ifferentiation by
{LEF}1-{M}ediated {WNT}1/b-{C}atenin {S}ignaling.},
journal = {Frontiers in cell and developmental biology},
volume = {8},
issn = {2296-634X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DZNE-2021-00120},
pages = {587778},
year = {2020},
note = {ISSN 2296-634X not unique: **3 hits**.},
abstract = {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.},
keywords = {Parkinson’s disease (Other) / dopamine (Other) / mouse
(Other) / nerve cell (Other) / regenerative therapy (Other)},
cin = {Ext HZM / AG Wurst},
ddc = {570},
cid = {I:(DE-2719)5000050 / I:(DE-2719)1140001},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:33195246},
pmc = {pmc:PMC7649324},
doi = {10.3389/fcell.2020.587778},
url = {https://pub.dzne.de/record/154266},
}