Embryonic development of selectively vulnerable neurons in Parkinson’s disease

Abstract A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative re...

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Autores principales:	Miguel A. P. Oliveira, Rudi Balling, Marten P. Smidt, Ronan M. T. Fleming
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/660046ffff8a480d94d9d334de4ddb98
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spelling	oai:doaj.org-article:660046ffff8a480d94d9d334de4ddb982021-12-02T15:10:26ZEmbryonic development of selectively vulnerable neurons in Parkinson’s disease10.1038/s41531-017-0022-42373-8057https://doaj.org/article/660046ffff8a480d94d9d334de4ddb982017-06-01T00:00:00Zhttps://doi.org/10.1038/s41531-017-0022-4https://doaj.org/toc/2373-8057Abstract A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease.Miguel A. P. OliveiraRudi BallingMarten P. SmidtRonan M. T. FlemingNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 3, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 Miguel A. P. Oliveira Rudi Balling Marten P. Smidt Ronan M. T. Fleming Embryonic development of selectively vulnerable neurons in Parkinson’s disease
description	Abstract A specific set of brainstem nuclei are susceptible to degeneration in Parkinson’s disease. We hypothesise that neuronal vulnerability reflects shared phenotypic characteristics that confer selective vulnerability to degeneration. Neuronal phenotypic specification is mainly the cumulative result of a transcriptional regulatory program that is active during the development. By manual curation of the developmental biology literature, we comprehensively reconstructed an anatomically resolved cellular developmental lineage for the adult neurons in five brainstem regions that are selectively vulnerable to degeneration in prodromal or early Parkinson’s disease. We synthesised the literature on transcription factors that are required to be active, or required to be inactive, in the development of each of these five brainstem regions, and at least two differentially vulnerable nuclei within each region. Certain transcription factors, e.g., Ascl1 and Lmx1b, seem to be required for specification of many brainstem regions that are susceptible to degeneration in early Parkinson’s disease. Some transcription factors can even distinguish between differentially vulnerable nuclei within the same brain region, e.g., Pitx3 is required for specification of the substantia nigra pars compacta, but not the ventral tegmental area. We do not suggest that Parkinson’s disease is a developmental disorder. In contrast, we consider identification of shared developmental trajectories as part of a broader effort to identify the molecular mechanisms that underlie the phenotypic features that are shared by selectively vulnerable neurons. Systematic in vivo assessment of fate determining transcription factors should be completed for all neuronal populations vulnerable to degeneration in early Parkinson’s disease.
format	article
author	Miguel A. P. Oliveira Rudi Balling Marten P. Smidt Ronan M. T. Fleming
author_facet	Miguel A. P. Oliveira Rudi Balling Marten P. Smidt Ronan M. T. Fleming
author_sort	Miguel A. P. Oliveira
title	Embryonic development of selectively vulnerable neurons in Parkinson’s disease
title_short	Embryonic development of selectively vulnerable neurons in Parkinson’s disease
title_full	Embryonic development of selectively vulnerable neurons in Parkinson’s disease
title_fullStr	Embryonic development of selectively vulnerable neurons in Parkinson’s disease
title_full_unstemmed	Embryonic development of selectively vulnerable neurons in Parkinson’s disease
title_sort	embryonic development of selectively vulnerable neurons in parkinson’s disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/660046ffff8a480d94d9d334de4ddb98
work_keys_str_mv	AT miguelapoliveira embryonicdevelopmentofselectivelyvulnerableneuronsinparkinsonsdisease AT rudiballing embryonicdevelopmentofselectivelyvulnerableneuronsinparkinsonsdisease AT martenpsmidt embryonicdevelopmentofselectivelyvulnerableneuronsinparkinsonsdisease AT ronanmtfleming embryonicdevelopmentofselectivelyvulnerableneuronsinparkinsonsdisease
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Embryonic development of selectively vulnerable neurons in Parkinson’s disease

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