Next Article in Journal
Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4
Next Article in Special Issue
Regulation of Adult Neurogenesis in Mammalian Brain
Previous Article in Journal
Hydroxytyrosol Inhibits Protein Oligomerization and Amyloid Aggregation in Human Insulin
Previous Article in Special Issue
Transcriptional Regulators and Human-Specific/Primate-Specific Genes in Neocortical Neurogenesis
Open AccessReview

Acquisition of the Midbrain Dopaminergic Neuronal Identity

Swammerdam Institute for Life Sciences, FNWI, University of Amsterdam, 1098 XH Amsterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4638; https://doi.org/10.3390/ijms21134638
Received: 25 May 2020 / Revised: 22 June 2020 / Accepted: 26 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Role of Gene Expression in the Physiology and Pathology of Neurons)
The mesodiencephalic dopaminergic (mdDA) group of neurons comprises molecularly distinct subgroups, of which the substantia nigra (SN) and ventral tegmental area (VTA) are the best known, due to the selective degeneration of the SN during Parkinson’s disease. However, although significant research has been conducted on the molecular build-up of these subsets, much is still unknown about how these subsets develop and which factors are involved in this process. In this review, we aim to describe the life of an mdDA neuron, from specification in the floor plate to differentiation into the different subsets. All mdDA neurons are born in the mesodiencephalic floor plate under the influence of both SHH-signaling, important for floor plate patterning, and WNT-signaling, involved in establishing the progenitor pool and the start of the specification of mdDA neurons. Furthermore, transcription factors, like Ngn2, Ascl1, Lmx1a, and En1, and epigenetic factors, like Ezh2, are important in the correct specification of dopamine (DA) progenitors. Later during development, mdDA neurons are further subdivided into different molecular subsets by, amongst others, Otx2, involved in the specification of subsets in the VTA, and En1, Pitx3, Lmx1a, and WNT-signaling, involved in the specification of subsets in the SN. Interestingly, factors involved in early specification in the floor plate can serve a dual function and can also be involved in subset specification. Besides the mdDA group of neurons, other systems in the embryo contain different subsets, like the immune system. Interestingly, many factors involved in the development of mdDA neurons are similarly involved in immune system development and vice versa. This indicates that similar mechanisms are used in the development of these systems, and that knowledge about the development of the immune system may hold clues for the factors involved in the development of mdDA neurons, which may be used in culture protocols for cell replacement therapies. View Full-Text
Keywords: mdDA neuronal development; floor plate patterning; DA progenitor; neuronal differentiation; subset specification mdDA neuronal development; floor plate patterning; DA progenitor; neuronal differentiation; subset specification
Show Figures

Figure 1

MDPI and ACS Style

Mesman, S.; Smidt, M.P. Acquisition of the Midbrain Dopaminergic Neuronal Identity. Int. J. Mol. Sci. 2020, 21, 4638.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop