Dose-Dependent and Subset-Specific Regulation of Midbrain Dopaminergic Neuron Differentiation by LEF1-Mediated WNT1/b-Catenin Signaling

Frontiers in Cell and Developmental Biology
Parivash NouriNilima Prakash

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...Continue Reading

References

Sep 24, 1999·Mechanisms of Development·A P MonaghanC Niehrs
Mar 11, 2003·Proceedings of the National Academy of Sciences of the United States of America·Silvia MarettoStefano Piccolo
May 4, 2004·Molecular and Cellular Neurosciences·Markus PanhuysenWolfgang Wurst
Oct 7, 2004·Gene Expression Patterns : GEP·Tomi JukkolaJuha Partanen
Oct 28, 2005·Nature·Dieter-Chichung LieFred H Gage
Jul 18, 2006·Nucleic Acids Research·Johannes RainerZlatko Trajanoski
Apr 3, 2007·Trends in Neurosciences·Wolfram Schultz
Apr 11, 2008·Molecular Biology of the Cell·Kyung-Ah KimArie Abo
Jan 6, 2009·Nature Neuroscience·Milan JoksimovicRajeshwar B Awatramani
Jun 16, 2009·Lancet·Andrew J LeesTamas Revesz
Oct 2, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Gonçalo Castelo-BrancoErnest Arenas
Oct 21, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Sebastian StuebnerNilima Prakash
Nov 20, 2009·The International Journal of Developmental Biology·Michela Di SalvioAntonio Simeone
Dec 5, 2009·Current Protocols in Stem Cell Biology·Jan PruszakGuido Nikkhah
Apr 16, 2010·Nature·Yutaka ShimomuraAngela M Christiano
May 27, 2010·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Andreas RatzkaAndrea Vortkamp
Jul 9, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mianzhi TangEric J Huang
Jun 30, 2011·The Journal of Comparative Neurology·Lindsay HayesSohyun Ahn
Sep 9, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Changgeng PengWeidong Le
Nov 25, 2011·Critical Reviews in Eukaryotic Gene Expression·Catherine D Mao, Stephen W Byers
Jan 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Emma R AnderssonErnest Arenas
Nov 30, 2013·Journal of Molecular Cell Biology·Milan Joksimovic, Rajeshwar Awatramani
Dec 12, 2013·Journal of Molecular Cell Biology·Wolfgang Wurst, Nilima Prakash
Jul 30, 2014·Cellular and Molecular Life Sciences : CMLS·Jesse V Veenvliet, Marten P Smidt

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
genotyping
PCR
Protein Assay
ChIP
Transfection
Assay
ChIP-PCR

Software Mentioned

Matrix Family Library
R R Core Team
ImageJ
Adobe Photoshop
Fluoview FV1000
LAS X
GePS
GraphPad Prism
CARMAweb
Axiovision

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Amygdala and Midbrain Dopamine

The midbrain dopamine system is widely studied for its involvement in emotional and motivational behavior. Some of these neurons receive information from the amygdala and project throughout the cortex. When the circuit and transmission of dopamine is disrupted symptoms may present. Here is the latest research on the amygdala and midbrain dopamine.

Cadherins and Catenins

Cadherins (named for "calcium-dependent adhesion") are a type of cell adhesion molecule (CAM) that is important in the formation of adherens junctions to bind cells with each other. Catenins are a family of proteins found in complexes with cadherin cell adhesion molecules of animal cells: alpha-catenin can bind to β-catenin and can also bind actin. β-catenin binds the cytoplasmic domain of some cadherins. Discover the latest research on cadherins and catenins here.

Adherens Junctions

An adherens junction is defined as a cell junction whose cytoplasmic face is linked to the actin cytoskeleton. They can appear as bands encircling the cell (zonula adherens) or as spots of attachment to the extracellular matrix (adhesion plaques). Adherens junctions uniquely disassemble in uterine epithelial cells to allow the blastocyst to penetrate between epithelial cells. Discover the latest research on adherens junctions here.

© 2021 Meta ULC. All rights reserved