ArticleThe Journal of biological chemistry2012
Cooperation of nuclear fibroblast growth factor receptor 1 and Nurr1 offers new interactive mechanism in postmitotic development of mesencephalic dopaminergic neurons.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Prenatal diagnosis and molecular cytogenetic characterization of 12 cases of chromosome 8 inverted duplication deletion syndrome.Orphanet journal of rare diseases · 2025Article
- N-glycosylation acts as a switch for FGFR1 trafficking between the plasma membrane and nuclear envelope.Cell communication and signaling : CCS · 2023Article
- FGF8-FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner.Disease models & mechanisms · 2022Article
- Fibroblast Growth Factor Signalling in the Diseased Nervous System.Molecular neurobiology · 2021Review
- The Role of Nuclear Insulin and IGF1 Receptors in Metabolism and Cancer.Biomolecules · 2021Review
- The transcription factor Nurr1 is upregulated in amyotrophic lateral sclerosis patients and SOD1-G93A mice.Disease models & mechanisms · 2020Article
- Cutting Edge Therapeutic Insights Derived from Molecular Biology of Pediatric High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG).Bioengineering (Basel, Switzerland) · 2018Review
- Cerebral organoids reveal early cortical maldevelopment in schizophrenia-computational anatomy and genomics, role of FGFR1.Translational psychiatry · 2017Article
- Common developmental genome deprogramming in schizophrenia - Role of Integrative Nuclear FGFR1 Signaling (INFS).Schizophrenia research · 2017Article
- Evidence-Based Theory for Integrated Genome Regulation of Ontogeny--An Unprecedented Role of Nuclear FGFR1 Signaling.Journal of cellular physiology · 2016Review
- Cryptic de novo deletion at 2q23.3-q24.1 in a patient with intellectual disability.Journal of genetics · 2016Article
- Nur77 Was Essential for Neurite Outgrowth and Involved in Schwann Cell Differentiation After Sciatic Nerve Injury.Journal of molecular neuroscience : MN · 2015Article
- Nurr1 blocks the mitogenic effect of FGF-2 and EGF, inducing olfactory bulb neural stem cells to adopt dopaminergic and dopaminergic-GABAergic neuronal phenotypes.Developmental neurobiology · 2015Article
- A nuclear odyssey: fibroblast growth factor-2 (FGF-2) as a regulator of nuclear homeostasis in the nervous system.Cellular and molecular life sciences : CMLS · 2015Review
- Membrane and integrative nuclear fibroblastic growth factor receptor (FGFR) regulation of FGF-23.The Journal of biological chemistry · 2015Article
- Article
- Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1).PloS one · 2015Article
- Receptor tyrosine kinases in the nucleus.Cold Spring Harbor perspectives in biology · 2013Review
- Activation of developmental nuclear fibroblast growth factor receptor 1 signaling and neurogenesis in adult brain by α7 nicotinic receptor agonist.Stem cells translational medicine · 2013Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Experiments in mice deficient for Nurr1 or expressing the dominant-negative FGF receptor (FGFR) identified orphan nuclear receptor Nurr1 and FGFR1 as essential factors in development of mesencephalic dopaminergic (mDA) neurons. FGFR1 affects brain cell development by two distinct mechanisms. Activation of cell surface FGFR1 by secreted FGFs stimulates proliferation of neural progenitor cells, whereas direct integrative nuclear FGFR1 signaling (INFS) is associated with an exit from the cell cycle and neuronal differentiation. Both Nurr1 and INFS activate expression of neuronal genes, such as tyrosine hydroxylase (TH), which is the rate-limiting enzyme in dopamine synthesis. Here, we show that nuclear FGFR1 and Nurr1 are expressed in the nuclei of developing TH-positive cells in the embryonic ventral midbrain. Both nuclear receptors were effectively co-immunoprecipitated from the ventral midbrain of FGF-2-deficient embryonic mice, which previously showed an increase of mDA neurons and enhanced nuclear FGFR1 accumulation. Immunoprecipitation and co-localization experiments showed the presence of Nurr1 and FGFR1 in common nuclear protein complexes. Fluorescence recovery after photobleaching and chromatin immunoprecipitation experiments demonstrated the Nurr1-mediated shift of nuclear FGFR1-EGFP mobility toward a transcriptionally active population and that both Nurr1 and FGFR1 bind to a common region in the TH gene promoter. Furthermore, nuclear FGFR1 or its 23-kDa FGF-2 ligand (FGF-2(23)) enhances Nurr1-dependent activation of the TH gene promoter. Transcriptional cooperation of FGFR1 with Nurr1 was confirmed on isolated Nurr1-binding elements. The proposed INFS/Nurr1 nuclear partnership provides a novel mechanism for TH gene regulation in mDA neurons and a potential therapeutic target in neurodevelopmental and neurodegenerative disorders.
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