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

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Brodski , C , Blaess , S , Partanen , J & Prakash , N 2019 , ' Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells ' , Journal of Developmental Biology , vol. 7 , no. 1 , 3 . https://doi.org/10.3390/jdb7010003

Title: Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells
Author: Brodski, Claude; Blaess, Sandra; Partanen, Juha; Prakash, Nilima
Contributor: University of Helsinki, Molecular and Integrative Biosciences Research Programme
Date: 2019-01-15
Language: eng
Number of pages: 34
Belongs to series: Journal of Developmental Biology
ISSN: 2221-3759
URI: http://hdl.handle.net/10138/312048
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.
Subject: dopamine
neuron
FGF8
SHH
WNT
BMP
Parkinson's disease
pluripotent stem cells
iPSC
BONE MORPHOGENETIC PROTEINS
VENTRAL TEGMENTAL AREA
FIBROBLAST GROWTH FACTOR-20
HUMAN INDUCED PLURIPOTENT
FLOOR PLATE
SONIC-HEDGEHOG
WNT/BETA-CATENIN
SUBSTANTIA-NIGRA
PARKINSONS-DISEASE
BETA-CATENIN
1184 Genetics, developmental biology, physiology
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