Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells

Brodski, Claude; Blaess, Sandra; Partanen, Juha; Prakash, Nilima

doi:10.3390/jdb7010003

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Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells

^1,*,

^2,*,

^3,* and

^4,*

Department of Physiology and Cell Biology, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be’er Sheva 84105, Israel

Institute of Reconstructive Neurobiology, University of Bonn Medical Center, 53127 Bonn, Germany

Faculty of Biological and Environmental Sciences, FIN00014-University of Helsinki, P.O. Box 56, Viikinkaari 9, FIN-00014 Helsinki, Finland

⁴

Department Hamm 2, Hamm-Lippstadt University of Applied Sciences, 59063 Hamm, Germany

Authors to whom correspondence should be addressed.

J. Dev. Biol. 2019, 7(1), 3; https://doi.org/10.3390/jdb7010003

Received: 30 November 2018 / Revised: 7 January 2019 / Accepted: 9 January 2019 / Published: 15 January 2019

(This article belongs to the Special Issue Crosstalk between FGF, TGF-β, BMP, and Wnt Signaling Pathways during Development)

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Abstract

Dopamine-synthesizing neurons located in the mammalian ventral midbrain are at the center stage of biomedical research due to their involvement in severe human neuropsychiatric and neurodegenerative disorders, most prominently Parkinson’s Disease (PD). The induction of midbrain dopaminergic (mDA) neurons depends on two important signaling centers of the mammalian embryo: the ventral midline or floor plate (FP) of the neural tube, and the isthmic organizer (IsO) at the mid-/hindbrain boundary (MHB). Cells located within and close to the FP secrete sonic hedgehog (SHH), and members of the wingless-type MMTV integration site family (WNT1/5A), as well as bone morphogenetic protein (BMP) family. The IsO cells secrete WNT1 and the fibroblast growth factor 8 (FGF8). Accordingly, the FGF8, SHH, WNT, and BMP signaling pathways play crucial roles during the development of the mDA neurons in the mammalian embryo. Moreover, these morphogens are essential for the generation of stem cell-derived mDA neurons, which are critical for the modeling, drug screening, and cell replacement therapy of PD. This review summarizes our current knowledge about the functions and crosstalk of these signaling pathways in mammalian mDA neuron development in vivo and their applications in stem cell-based paradigms for the efficient derivation of these neurons in vitro. View Full-Text

Keywords: dopamine; neuron; FGF8; SHH; WNT; BMP; Parkinson’s disease; pluripotent stem cells; iPSC

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Brodski, C.; Blaess, S.; Partanen, J.; Prakash, N. Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells. J. Dev. Biol. 2019, 7, 3. https://doi.org/10.3390/jdb7010003

AMA Style

Brodski C, Blaess S, Partanen J, Prakash N. Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells. Journal of Developmental Biology. 2019; 7(1):3. https://doi.org/10.3390/jdb7010003

Chicago/Turabian Style

Brodski, Claude, Sandra Blaess, Juha Partanen, and Nilima Prakash. 2019. "Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells" Journal of Developmental Biology 7, no. 1: 3. https://doi.org/10.3390/jdb7010003

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Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells

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