ArticleStem cells and development2015
Thyroid Hormone-Otx2 Signaling Is Required for Embryonic Ventral Midbrain Neural Stem Cells Differentiated into Dopamine Neurons.
Article in Stem cells and development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 30 citations in OpenAlex.
- A study of the correlation between cognitive function and thyroid hormones in patients with Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- Early-life stress sensitizes response to future stress: Evidence and mechanisms.Neurobiology of stress · 2025Review
- Molecular heterogeneity and development of the ventral tegmental area.Current opinion in behavioral sciences · 2025Article
- Manganese exposure induces parkinsonism-like symptoms by Serpina3n-TFEB-v/p-ATPase signaling mediated lysosomal dysfunction.Cell biology and toxicology · 2025Article
- Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior.Hormones and behavior · 2024Article
- Local Thyroid Hormone Action in Brain Development.International journal of molecular sciences · 2023Review
- Review
- Deep learning-based predictive identification of neural stem cell differentiation.Nature communications · 2021Article
- Synergic Effects of Berberine and Curcumin on Improving Cognitive Function in an Alzheimer's Disease Mouse Model.Neurochemical research · 2020Article
- Dopamine neuron induction and the neuroprotective effects of thyroid hormone derivatives.Scientific reports · 2019Article
- Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects.Frontiers in molecular neuroscience · 2019Article
- Nuclear receptors in neural stem/progenitor cell homeostasis.Cellular and molecular life sciences : CMLS · 2017Review
- TLR4 Activation Promotes Bone Marrow MSC Proliferation and Osteogenic Differentiation via Wnt3a and Wnt5a Signaling.PloS one · 2016Article
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Authors and funding
14 authors at 2 institutions in 1 country.
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Abstract
Midbrain dopamine (DA) neurons are essential for maintaining multiple brain functions. These neurons have also been implicated in relation with diverse neurological disorders. However, how these neurons are developed from neuronal stem cells (NSCs) remains largely unknown. In this study, we provide both in vivo and in vitro evidence that the thyroid hormone, an important physiological factor for brain development, promotes DA neuron differentiation from embryonic ventral midbrain (VM) NSCs. We find that thyroid hormone deficiency during development reduces the midbrain DA neuron number, downregulates the expression of tyrosine hydroxylase (TH) and the dopamine transporter (DAT), and impairs the DA neuron-dependent motor behavior. In addition, thyroid hormone treatment during VM NSC differentiation in vitro increases the production of DA neurons and upregulates the expression of TH and DAT. We also found that the thyroid hormone enhances the expression of Otx2, an important determinant of DA neurogenesis, during DA neuron differentiation. Our in vitro gene silencing experiments indicate that Otx2 is required for thyroid hormone-dependent DA neuron differentiation from embryonic VM NSCs. Finally, we revealed both in vivo and in vitro that the thyroid hormone receptor alpha 1 is expressed in embryonic VM NSCs. Furthermore, it participates in the effects of thyroid hormone-induced Otx2 upregulation and DA neuron differentiation. These data demonstrate the role and molecular mechanisms of how the thyroid hormone regulates DA neuron differentiation from embryonic VM NSCs, particularly providing new mechanisms and a potential strategy for generating dopamine neurons from NSCs.
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