ArticleProceedings of the National Academy of Sciences of the United States of America2009
Spatiotemporally separable Shh domains in the midbrain define distinct dopaminergic progenitor pools.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed.
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- Exercise combined with induced pluripotent stem cells enhances the Wnt1-Lmx1a loop in the midbrain of Parkinsonian mice to alleviate Parkinsonian symptoms.World journal of stem cells · 2025Article
- Specification of human brain regions with orthogonal gradients of WNT and SHH in organoids reveals patterning variations across cell lines.Cell stem cell · 2025Article
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- Molecular and spatial transcriptomic classification of midbrain dopamine neurons and their alterations in a LRRK2bioRxiv : the preprint server for biology · 2024Article
- Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development.Nature communications · 2024Article
- A novel mutation in intron 1 of Wnt1 causes developmental loss of dopaminergic neurons in midbrain and ASD-like behaviors in rats.Molecular psychiatry · 2023Article
- Comprehensive spatiotemporal mapping of single-cell lineages in developing mouse brain by CRISPR-based barcoding.Nature methods · 2023Article
- Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke.Cell death discovery · 2023Review
- Development, wiring and function of dopamine neuron subtypes.Nature reviews. Neuroscience · 2023Review
- CRISPR/Cas9-based QF2 knock-in at theFrontiers in neuroanatomy · 2023Article
- Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson's disease in the rat.Journal of neuroinflammation · 2022Article
- Identification of ASCL1 as a determinant for human iPSC-derived dopaminergic neurons.Scientific reports · 2021Article
- Sox6 expression distinguishes dorsally and ventrally biased dopamine neurons in the substantia nigra with distinctive properties and embryonic origins.Cell reports · 2021Article
- Human neural organoids: Models for developmental neurobiology and disease.Developmental biology · 2021Review
- A dynamical model for the basal ganglia-thalamo-cortical oscillatory activity and its implications in Parkinson's disease.Cognitive neurodynamics · 2021Article
- On the Road from Phenotypic Plasticity to Stem Cell Therapy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Current State-of-the-Art and Unresolved Problems in Using Human Induced Pluripotent Stem Cell-Derived Dopamine Neurons for Parkinson's Disease Drug Development.International journal of molecular sciences · 2021Review
12 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
Midbrain dopamine neurons (mDA) are important regulators of diverse physiological functions, including movement, attention, and reward behaviors. Accordingly, aberrant function of dopamine neurons underlies a wide spectrum of disorders, such as Parkinson's disease (PD), dystonia, and schizophrenia. The distinct functions of the dopamine system are carried out by neuroanatomically discrete subgroups of dopamine neurons, which differ in gene expression, axonal projections, and susceptibility in PD. The developmental underpinnings of this heterogeneity are undefined. We have recently shown that in the embryonic CNS, mDA originate from the midbrain floor plate, a ventral midline structure that is operationally defined by the expression of the molecule Shh. Here, we develop these findings to reveal that in the embryonic midbrain, the spatiotemporally dynamic Shh domain defines multiple progenitor pools. We deduce 3 distinct progenitor pools, medial, intermediate, and lateral, which contribute to different mDA clusters. The earliest progenitors to express Shh, here referred to as the medial pool, contributes neurons to the rostral linear nucleus and mDA of the ventral tegmental area/interfascicular regions, but remarkably, little to the substantia nigra pars compacta. The intermediate Shh+ progenitors give rise to neurons of all dopaminergic nuclei, including the SNpc. The last and lateral pool of Shh+ progenitors generates a cohort that populates the red nucleus, Edinger Westphal nucleus, and supraoculomotor nucleus and cap. Subsequently, these lateral Shh+ progenitors produce mDA. This refined ontogenetic definition will expand understanding of dopamine neuron biology and selective susceptibility, and will impact stem cell-derived therapies and models for PD.
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