Cited by 587Pluripotent Stem Cells ResearchNeurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene Regulation

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Identification of Intrinsic Determinants of Midbrain Dopamine Neurons

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Andersson, Elisabet, Tryggvason, Ulrika, Deng, Qiaolin, Friling, Stina, Alekseenko, Zhanna, Robert, Benoit, Perlmann, Thomas, Ericson, Johan·2006·Cell

DOI 10.1016/j.cell.2005.10.037

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Abstract

The prospect of using cell replacement therapies has raised the key issue of whether elucidation of developmental pathways can facilitate the generation of therapeutically important cell types from stem cells. Here we show that the homeodomain proteins Lmx1a and Msx1 function as determinants of midbrain dopamine neurons, cells that degenerate in patients with Parkinson's disease. Lmx1a is sufficient and required to trigger dopamine cell differentiation. An early activity of Lmx1a is to induce the expression of Msx1, which complements Lmx1a by inducing the proneural protein Ngn2 and neuronal differentiation. Importantly, expression of Lmx1a in embryonic stem cells results in a robust generation of dopamine neurons with a "correct" midbrain identity. These data establish that Lmx1a and Msx1 are critical intrinsic dopamine-neuron determinants in vivo and suggest that they may be essential tools in cell replacement strategies in Parkinson's disease.

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Authors: Andersson, E., Tryggvason, U., Deng, Q., Friling, S., Alekseenko, Z., Robert, B., Perlmann, T., & Ericson, J.
Affiliations: Karolinska Institutet (SE)
Ludwig Cancer Research (SE)
Corresponding author: Perlmann, Thomas
Ericson, Johan
ORCID: Andersson, Elisabet
Deng, Qiaolin
Alekseenko, Zhanna
Perlmann, Thomas
Ericson, Johan
Venue: Cell
Publisher: Elsevier BV
Published: 2006-01
Volume: 124
Issue: 2
Pages: 393-405
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2005.10.037
OpenAlex: W2111525324
Cited by: 587
References: 59
Citations by year: 2026: 14 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 14 · 2021: 18 · 2020: 22 · 2019: 18 · 2018: 19 · 2017: 21 · 2016: 26 · 2015: 29 · 2014: 22 · 2013: 45 · 2012: 48
FWCI: 22.83
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2790 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords: midbrain dopaminergic neurons, Lmx1a, MSX1, Ngn2, homeodomain transcription factor, neuronal differentiation, Parkinson's disease, cell replacement therapy, embryonic stem cells, proneural genes
MeSH terms: Animals, Cells, Cultured, Chick Embryo, Dopamine, Mesencephalon, Neurons, Stem Cells, Transcription Factors, Signal Transduction, Trans-Activators, Homeodomain Proteins, Embryo Research, Mice, MSX1 Transcription Factor, Hedgehog Proteins, LIM-Homeodomain Proteins

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Identification of Intrinsic Determinants of Midbrain Dopamine Neurons

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