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4 results on '"Di Giovannantonio, L. G."'

1. A neuronal migratory pathway crossing from diencephalon to telencephalon populates amygdala nuclei

Author

García-Moreno, Fernando, Pedraza Boti, María, Di Giovannantonio, L. G., Di Salvio, M., López-Mascaraque, Laura, Simeone, Antonio, Carlos, Juan A. de, García-Moreno, Fernando, Pedraza Boti, María, Di Giovannantonio, L. G., Di Salvio, M., López-Mascaraque, Laura, Simeone, Antonio, and Carlos, Juan A. de

Abstract

Neurons usually migrate and differentiate in one particular encephalic vesicle. We identified a murine population of diencephalic neurons that colonized the telencephalic amygdaloid complex, migrating along a tangential route that crosses a boundary between developing brain vesicles. The diencephalic transcription factor OTP was necessary for this migratory behavior. © 2010 Nature America, Inc. All rights reserved.

Published
2010

3. Serotonin Hyperinnervation Abolishes Seizure Susceptibility in Otx2 Conditional Mutant Mice

Author

Tripathi PP, Di Giovannantonio LG, Viegi A, Wurst W, Simeone A, Bozzi Y. Tripathi PP, Bozzi Y, TRIPATHI P., P, DI GIOVANNANTONIO L., G, Viegi, Alessandro, Wurst, W, Simeone, A, and Bozzi, Y.

Subjects
medicine.medical_specialty, Kainic acid, Serotonin, Time Factors, Transgene, Cre recombinase, Hippocampus, Mice, Transgenic, Biology, Serotonergic, chemistry.chemical_compound, Mice, Mesencephalon, Seizures, Internal medicine, FLOX, medicine, Animals, RNA, Messenger, Enzyme Inhibitors, Homeodomain Proteins, Serotonin Plasma Membrane Transport Proteins, Analysis of Variance, Kainic Acid, Otx Transcription Factors, General Neuroscience, Glutamate receptor, Fenclonine, Mice, Inbred C57BL, Endocrinology, chemistry, Gene Expression Regulation, Mutation, Brief Communications, Proto-Oncogene Proteins c-fos
Abstract

The homeobox-containing transcription factor Otx2 is crucially involved in fate determination of midbrain neurons. Mutant mice, in whichOtx2was conditionally inactivated by a Cre recombinase expressed under the transcriptional control of the Engrailed1 (En1) gene (En1cre/+;Otx2flox/flox), show a reduced number of dopaminergic neurons and an increased number of serotonergic neurons in the ventral midbrain. Despite these developmental anatomical alterations,En1cre/+;Otx2flox/floxadult mice display normal motor function. Here, we further investigated the neurological consequences ofOtx2inactivation in adultEn1cre/+;Otx2flox/floxmice. AdultEn1cre/+;Otx2flox/floxmice showed increased serotonin (5-HT) levels in the pons, ventral midbrain, hippocampus (CA3 subfield), and cerebral cortex, as indicated by HPLC and immunohistochemistry. Conversely, SERT (5-HT transporter) levels were decreased in conditional mutant brains. As a consequence of this increased 5-HT hyperinnervation,En1cre/+;Otx2flox/floxmice were resistant to generalized seizures induced by the glutamate agonist kainic acid (KA). Indeed, prolonged pretreatment ofEn1cre/+;Otx2flox/floxmice with the 5-HT synthesis inhibitorpara-chlorophenylalanine (pCPA) restored brain 5-HT content to control levels, fully reestablishing KA seizure susceptibility. Accordingly, c-fosmRNA induction after KA was restricted to the hippocampus inEn1cre/+;Otx2flox/floxmice, whereas a widespread c-fosmRNA labeling was observed throughout the brain ofEn1cre/+;Otx2flox/floxmice pretreated with pCPA. These results clearly show that increased brain 5-HT levels are responsible for seizure resistance inEn1cre/+;Otx2flox/floxmice and confirm the important role of 5-HT in the control of seizure spread.

Published
2008
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4. Increased dopaminergic innervation in the brain of conditional mutant mice overexpressing Otx2: effects on locomotor behavior and seizure susceptibility.

Author

Tripathi PP, Di Giovannantonio LG, Sanguinetti E, Acampora D, Allegra M, Caleo M, Wurst W, Simeone A, and Bozzi Y

Subjects
Animals, Brain physiopathology, Cell Count, Dopamine Plasma Membrane Transport Proteins metabolism, Kainic Acid, Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Transgenic, Neural Pathways physiology, Otx Transcription Factors genetics, Parvalbumins metabolism, Proto-Oncogene Proteins c-fos metabolism, Proto-Oncogene Proteins c-jun metabolism, RNA, Messenger metabolism, Brain cytology, Brain physiology, Dopamine metabolism, Dopaminergic Neurons physiology, Motor Activity physiology, Otx Transcription Factors metabolism, Seizures physiopathology
Abstract

The homeobox-containing transcription factor Otx2 controls the identity, fate and proliferation of mesencephalic dopaminergic (mesDA) neurons. Transgenic mice, in which Otx2 was conditionally overexpressed by a Cre recombinase expressed under the transcriptional control of the Engrailed1 gene (En1(Cre/+); tOtx2(ov/+)), show an increased number of mesDA neurons during development. In adult mice, Otx2 is expressed in a subset of neurons in the ventral tegmental area (VTA) and its overexpression renders mesDA more resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-HCl (MPTP) neurotoxin. Here we further investigated the neurological consequences of the increased number of mesDA neurons in En1(Cre/+); tOtx2(ov/+) adult mice. Immunohistochemistry for the active, glycosylated form of the dopamine transporter (glyco-Dat) showed that En1(Cre/+); tOtx2(ov/+) adult mice display an increased density of mesocortical DAergic fibers, as compared to control animals. Increased glyco-Dat staining was accompanied by a marked hypolocomotion in En1(Cre/+); tOtx2(ov/+) mice, as detected in the open field test. Since conditional knockout mice lacking Otx2 in mesDA precursors (En1(Cre/+); Otx2(floxv/flox) mice) show a marked resistance to kainic acid (KA)-induced seizures, we investigated the behavioral response to KA in En1(Cre/+); tOtx2(ov/+) and control mice. No difference was observed between mutant and control mice, but En1(Cre/+); tOtx2(ov/+) mice showed a markedly different c-fos mRNA induction profile in the cerebral cortex and hippocampus after KA seizures, as compared to controls. Accordingly, an increased density of parvalbumin (PV)-positive inhibitory interneurons was detected in the deep layers of the frontal cortex of naïve En1(Cre/+); tOtx2(ov/+) mice, as compared to controls. These data indicate that Otx2 overexpression results in increased DAergic innervation and PV cell density in the fronto-parietal cortex, with important consequences on spontaneous locomotor activity and seizure-induced gene expression. Our results strengthen the notion that Otx2 mutant mouse models are a powerful genetic tool to unravel the molecular and behavioral consequences of altered development of the DAergic system., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Published
2014
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