PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Nouri, P.* ; Götz, S. ; Rauser, B. ; Irmler, M. ; Peng, C. ; Trümbach, D. ; Kempny, C.* ; Lechermeier, C.G. ; Bryniok, A.* ; Dlugos, A.* ; Euchner, E.* ; Beckers, J. ; Brodski, C.* ; Klümper, C.* ; Wurst, W. ; Prakash, N.*

Dose-dependent and subset-specific regulation of midbrain dopaminergic neuron differentiation by LEF1-mediated WNT1/b-catenin signaling.

Front. Cell Dev. Biol. 8:587778 (2020)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
5.201
1.288
4
6
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Dopamine ; Nerve Cell ; Parkinson’ ; S Disease ; Regenerative Therapy ; Mouse; Ventral Tegmental Area; Sonic-hedgehog; Beta-catenin; Network Controls; Multiple Roles; In-vivo; Expression; Neurogenesis; Progenitors; Promotes
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 2296-634X
e-ISSN 2296-634X
Zeitschrift Frontiers in cell and developmental biology
Quellenangaben Band: 8, Heft: , Seiten: , Artikelnummer: 587778 Supplement: ,
Verlag Frontiers
Verlagsort Lausanne
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
Institute of Experimental Genetics (IEG)
POF Topic(s) 30204 - Cell Programming and Repair
30201 - Metabolic Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
G-500600-004
Förderungen National Natural Science Foundation of China
United States - Israel Binational Science Foundation
Israel Science Foundation
Helmholtz Association (Alliance "Aging and Metabolic Programming, AMPro")
Deutsche Forschungsgemeinschaft [Munich Cluster for Systems Neurology]
Deutsche Forschungsgemeinschaft [Collaborative Research Centre]
Deutsche Forschungsgemeinschaft
DOI 10.3389/fcell.2020.587778
WOS ID WOS:000587391800001
Scopus ID 85095690986
PubMed ID 33195246
Erfassungsdatum 2020-11-05
[➜Korrektur melden]