ArticlePloS one2015
Otx2 Requires Lmx1b to Control the Development of Mesodiencephalic Dopaminergic Neurons.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 30 citations in OpenAlex.
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- Multiomics analysis identifies novel facilitators of human dopaminergic neuron differentiation.EMBO reports · 2024Article
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- On the Use of Heterogeneous Stock Mice to Map Transcriptomes Associated With Excessive Ethanol Consumption.Frontiers in psychiatry · 2021Review
- Paroxysmal Cranial Dyskinesia and Nail-Patella Syndrome Caused by a Novel Variant in the LMX1B Gene.Movement disorders : official journal of the Movement Disorder Society · 2020Article
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- Homeoprotein OTX1 and OTX2 involvement in rat myenteric neuron adaptation after DNBS-induced colitis.PeerJ · 2020Article
- Crosstalk of Intercellular Signaling Pathways in the Generation of Midbrain Dopaminergic Neurons In Vivo and from Stem Cells.Journal of developmental biology · 2019Review
- EZH2 Is Essential for Fate Determination in the Mammalian Isthmic Area.Frontiers in molecular neuroscience · 2019Article
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- Lmx1a is required for the development of the ovarian stem cell niche inDevelopment (Cambridge, England) · 2018Article
- BMP/SMAD Pathway Promotes Neurogenesis of Midbrain Dopaminergic NeuronsThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Developmental pathway genes and neural plasticity underlying emotional learning and stress-related disorders.Learning & memory (Cold Spring Harbor, N.Y.) · 2017Review
- Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool.Frontiers in molecular neuroscience · 2017Article
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Authors and funding
8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Studying the development of mesodiencephalic dopaminergic (mdDA) neurons provides an important basis for better understanding dopamine-associated brain functions and disorders and is critical for establishing cell replacement therapy for Parkinson's disease. The transcription factors Otx2 and Lmx1b play a key role in the development of mdDA neurons. However, little is known about the genes downstream of Otx2 and Lmx1b in the pathways controlling the formation of mdDA neurons in vivo. Here we report on our investigation of Lmx1b as downstream target of Otx2 in the formation of mdDA neurons. Mouse mutants expressing Otx2 under the control of the En1 promoter (En1+/Otx2) showed increased Otx2 expression in the mid-hindbrain region, resulting in upregulation of Lmx1b and expansion of mdDA neurons there. In contrast, Lmx1b-/- mice showed decreased expression of Otx2 and impairments in several aspects of mdDA neuronal formation. To study the functional interaction between Otx2 and Lmx1b, we generated compound mutants in which Otx2 expression was restored in mice lacking Lmx1b (En1+/Otx2;Lmx1b-/-). In these animals Otx2 was not sufficient to rescue any of the aberrations in the formation of mdDA neurons caused by the loss of Lmx1b, but rescued the loss of ocular motor neurons. Gene expression studies in Lmx1b-/- embryos indicated that in these mutants Wnt1, En1 and Fgf8 expression are induced but subsequently lost in the mdDA precursor domain and the mid-hindbrain organizer in a specific, spatio-temporal manner. In summary, we demonstrate that Otx2 critically depends on Lmx1b for the formation of mdDA neurons, but not for the generation of ocular motor neurons. Moreover, our data suggest that Lmx1b precisely maintains the expression pattern of Wnt1, Fgf8 and En1, which are essential for mid-hindbrain organizer function and the formation of mdDA neurons.
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