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Molecular analysis of the midbrain dopaminergic niche during neurogenesis

Enrique M. Toledo, Gioele La Manno, Pia Rivetti di Val Cervo, View ORCID ProfileDaniel Gyllborg, Saiful Islam, Carlos Villaescusa, Sten Linnarsson, View ORCID ProfileErnest Arenas
doi: https://doi.org/10.1101/155846
Enrique M. Toledo
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Gioele La Manno
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Pia Rivetti di Val Cervo
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Daniel Gyllborg
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Saiful Islam
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Carlos Villaescusa
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Sten Linnarsson
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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Ernest Arenas
1 Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 1, 17177, Stockholm, Sweden
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ABSTRACT

Midbrain dopaminergic (mDA) neurons degenerate in Parkinson’s disease and are one of the main targets for cell replacement therapies. However, a comprehensive view of the signals and cell types contributing to mDA neurogenesis is not yet available. By analyzing the transcriptome of the mouse ventral midbrain at a tissue and single-cell level during mDA neurogenesis we found that three recently identified radial glia types 1-3 (Rgl1-3) contribute to different key aspects of mDA neurogenesis. While Rgl3 expressed most extracellular matrix components and multiple ligands for various pathways controlling mDA neuron development, such as Wnt and Shh, Rgl1-2 expressed most receptors. Moreover, we found that specific transcription factor networks explain the transcriptome and suggest a function for each individual radial glia. A network controlling neurogenesis was found in Rgl1, progenitor maintenance in Rgl2 and the secretion of factors forming the mDA niche by Rgl3. Our results thus uncover a broad repertoire of developmental signals expressed by each midbrain cell type during mDA neurogenesis. Cells identified for their emerging importance are Rgl3, a niche cell type, and Rgl1, a neurogenic progenitor that expresses ARNTL, a transcription factor that we find is required for mDA neurogenesis.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 26, 2017.
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Molecular analysis of the midbrain dopaminergic niche during neurogenesis
Enrique M. Toledo, Gioele La Manno, Pia Rivetti di Val Cervo, Daniel Gyllborg, Saiful Islam, Carlos Villaescusa, Sten Linnarsson, Ernest Arenas
bioRxiv 155846; doi: https://doi.org/10.1101/155846
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Molecular analysis of the midbrain dopaminergic niche during neurogenesis
Enrique M. Toledo, Gioele La Manno, Pia Rivetti di Val Cervo, Daniel Gyllborg, Saiful Islam, Carlos Villaescusa, Sten Linnarsson, Ernest Arenas
bioRxiv 155846; doi: https://doi.org/10.1101/155846

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