Acquisition of the Midbrain Dopaminergic Neuronal Identity.
Animals
Cell Differentiation
/ genetics
Dopamine
/ metabolism
Dopaminergic Neurons
/ metabolism
Embryo, Mammalian
/ cytology
Gene Expression Regulation, Developmental
/ genetics
Humans
Mesencephalon
/ cytology
Substantia Nigra
/ embryology
Transcription Factors
/ genetics
Ventral Tegmental Area
/ embryology
DA progenitor
floor plate patterning
mdDA neuronal development
neuronal differentiation
subset specification
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
30 Jun 2020
30 Jun 2020
Historique:
received:
25
05
2020
revised:
22
06
2020
accepted:
26
06
2020
entrez:
8
7
2020
pubmed:
8
7
2020
medline:
17
2
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32629812
pii: ijms21134638
doi: 10.3390/ijms21134638
pmc: PMC7369932
pii:
doi:
Substances chimiques
Transcription Factors
0
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
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