Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP
| Autor: | Luca Giovanni Di Giovannantonio, Antonio Simeone, Wolfgang Wurst, Raffaele Prosperi, Dario Acampora, Daniela Omodei, Michela Di Salvio, Nilima Prakash |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Identification prevention & control [MPTP Poisoning] cytology [Ventral Tegmental Area] Mice lacking physiology [Otx Transcription Factors] Mice chemistry.chemical_compound 0302 clinical medicine cytology [Embryonic Stem Cells] pathology [Neurons] Neurotoxin Gene-expression Neurons 0303 health sciences Otx Transcription Factors Trafficking biology General Neuroscience MPTP Dopaminergic pathology [Ventral Tegmental Area] physiology [Neurons] classification [Neurons] Ventral tegmental area Death medicine.anatomical_structure Mice Inbred DBA medicine.drug NURR1 metabolism [MPTP Poisoning] Mice Transgenic Substantia nigra Transporter pathology [MPTP Poisoning] pathology [Embryonic Stem Cells] 03 medical and health sciences Dopamine ddc:570 medicine Animals physiology [Ventral Tegmental Area] Embryonic Stem Cells 030304 developmental biology Dopamine transporter Ventral Tegmental Area Fate MPTP Poisoning Otx2 protein mouse physiology [Embryonic Stem Cells] Mice Inbred C57BL chemistry nervous system biology.protein Degeneration Midbrain dopaminergic-neurons Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Nature neuroscience 13 (2010): 1481–1488. doi:10.1038/nn.2661 info:cnr-pdr/source/autori:Di Salvio M.; Di Giovannantonio L.G.; Acampora D.; Prosperi R.; Omodei D.; Prakash N.; Wurst W.; Simeone A./titolo:Otx2 controls neuron subtype identity in ventral tegmental area and antagonizes vulnerability to MPTP/doi:10.1038%2Fnn.2661/rivista:Nature neuroscience (Print)/anno:2010/pagina_da:1481/pagina_a:1488/intervallo_pagine:1481–1488/volume:13 Nature reviews / Neuroscience 13(12), 1481-1488 (2010). doi:10.1038/nn.2661 Nature Neuroscience; Vol 13 |
| DOI: | 10.1038/nn.2661 |
| Popis: | Mesencephalic-diencephalic dopaminergic neurons control locomotor activity and emotion and are affected in neurodegenerative and psychiatric diseases. The homeoprotein Otx2 is restricted to ventral tegmental area (VTA) neurons that are prevalently complementary to those expressing Girk2 and glycosylated active form of the dopamine transporter (Dat). High levels of glycosylated Dat mark neurons with efficient dopamine uptake and pronounced vulnerability to Parkinsonian degeneration. We found that Otx2 controls neuron subtype identity by antagonizing molecular and functional features of dorsal-lateral VTA, such as Girk2 and Dat expression. Otx2 limited the number of VTA neurons with efficient dopamine uptake and conferred resistance to the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Ectopic Otx2 expression also provided neurons of the substantia nigra with efficient neuroprotection to MPTP. These findings indicate that Otx2 is required to specify neuron subtype identity in VTA and may antagonize vulnerability to the Parkinsonian toxin MPTP. |
| Databáze: | OpenAIRE |
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