A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo

N Prakash; C Brodski; T Naserke; E Puelles; R Gogoi; A Hall; M Panhuysen; D Echevarria; L Sussel; D M V Weisenhorn; S Martinez; E Arenas; A Simeone; W Wurst

doi:10.1242/dev.02181

A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo

N Prakash, C Brodski, T Naserke, E Puelles, R Gogoi, A Hall, M Panhuysen, D Echevarria, L Sussel, D M V Weisenhorn, S Martinez, E Arenas, A Simeone, W Wurst

King's College London

Research output: Contribution to journal › Article › peer-review

218 Citations (Scopus)

Abstract

Midbrain neurons synthesizing the neurotransmitter dopamine play a central role in the modulation of different brain functions and are associated with major neurological and psychiatric disorders. Despite the importance of these cells, the molecular mechanisms controlling their development are still poorly understood. The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons. Here, we show that Wnt1 regulates the genetic network, including Otx2 and Nkx2-2, that is required for the establishment of the midbrain dopaminergic progenitor domain during embryonic development. In addition, Wnt1 is required for the terminal differentiation of midbrain dopaminergic neurons at later stages of embryogenesis. These results identify Wnt1 as a key molecule in the development of midbrain dopaminergic neurons in vivo. They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease

Original language	English
Pages (from-to)	89 - 98
Number of pages	10
Journal	Development (Cambridge): for advances in developmental biology and stem cells
Volume	133
Issue number	1
DOIs	https://doi.org/10.1242/dev.02181
Publication status	Published - Jan 2006

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Prakash, N., Brodski, C., Naserke, T., Puelles, E., Gogoi, R., Hall, A., Panhuysen, M., Echevarria, D., Sussel, L., Weisenhorn, D. M. V., Martinez, S., Arenas, E., Simeone, A., & Wurst, W. (2006). A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development (Cambridge): for advances in developmental biology and stem cells, 133(1), 89 - 98. https://doi.org/10.1242/dev.02181

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title = "A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo",

abstract = "Midbrain neurons synthesizing the neurotransmitter dopamine play a central role in the modulation of different brain functions and are associated with major neurological and psychiatric disorders. Despite the importance of these cells, the molecular mechanisms controlling their development are still poorly understood. The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons. Here, we show that Wnt1 regulates the genetic network, including Otx2 and Nkx2-2, that is required for the establishment of the midbrain dopaminergic progenitor domain during embryonic development. In addition, Wnt1 is required for the terminal differentiation of midbrain dopaminergic neurons at later stages of embryogenesis. These results identify Wnt1 as a key molecule in the development of midbrain dopaminergic neurons in vivo. They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease",

author = "N Prakash and C Brodski and T Naserke and E Puelles and R Gogoi and A Hall and M Panhuysen and D Echevarria and L Sussel and Weisenhorn, {D M V} and S Martinez and E Arenas and A Simeone and W Wurst",

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Prakash, N, Brodski, C, Naserke, T, Puelles, E, Gogoi, R, Hall, A, Panhuysen, M, Echevarria, D, Sussel, L, Weisenhorn, DMV, Martinez, S, Arenas, E, Simeone, A & Wurst, W 2006, 'A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo', Development (Cambridge): for advances in developmental biology and stem cells, vol. 133, no. 1, pp. 89 - 98. https://doi.org/10.1242/dev.02181

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AU - Prakash, N

AU - Brodski, C

AU - Naserke, T

AU - Puelles, E

AU - Gogoi, R

AU - Hall, A

AU - Panhuysen, M

AU - Echevarria, D

AU - Sussel, L

AU - Weisenhorn, D M V

AU - Martinez, S

AU - Arenas, E

AU - Simeone, A

AU - Wurst, W

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N2 - Midbrain neurons synthesizing the neurotransmitter dopamine play a central role in the modulation of different brain functions and are associated with major neurological and psychiatric disorders. Despite the importance of these cells, the molecular mechanisms controlling their development are still poorly understood. The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons. Here, we show that Wnt1 regulates the genetic network, including Otx2 and Nkx2-2, that is required for the establishment of the midbrain dopaminergic progenitor domain during embryonic development. In addition, Wnt1 is required for the terminal differentiation of midbrain dopaminergic neurons at later stages of embryogenesis. These results identify Wnt1 as a key molecule in the development of midbrain dopaminergic neurons in vivo. They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease

AB - Midbrain neurons synthesizing the neurotransmitter dopamine play a central role in the modulation of different brain functions and are associated with major neurological and psychiatric disorders. Despite the importance of these cells, the molecular mechanisms controlling their development are still poorly understood. The secreted glycoprotein Wnt1 is expressed in close vicinity to developing midbrain dopaminergic neurons. Here, we show that Wnt1 regulates the genetic network, including Otx2 and Nkx2-2, that is required for the establishment of the midbrain dopaminergic progenitor domain during embryonic development. In addition, Wnt1 is required for the terminal differentiation of midbrain dopaminergic neurons at later stages of embryogenesis. These results identify Wnt1 as a key molecule in the development of midbrain dopaminergic neurons in vivo. They also suggest the Wnt1-controlled signaling pathway as a promising target for new therapeutic strategies in the treatment of Parkinson's disease

U2 - 10.1242/dev.02181

DO - 10.1242/dev.02181

M3 - Article

SN - 1477-9129

VL - 133

SP - 89

EP - 98

JO - Development (Cambridge): for advances in developmental biology and stem cells

JF - Development (Cambridge): for advances in developmental biology and stem cells

IS - 1

ER -

A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo

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