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Pitx3 regulates tyrosine hydroxylase expression in the substantia nigra and identifies a subgroup of mesencephalic dopaminergic progenitor neurons during mouse development.
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Recent studies of mouse mutant aphakia have implicated the homeobox gene Pitx3 in the survival of substantia nigra dopaminergic neurons, the degeneration of which causes Parkinson's disease. To directly investigate a role for Pitx3 in midbrain DA neuron development, we have analysed a line of
Stem cell grafting improves both motor and cognitive impairments in a genetic model of Parkinson's disease, the aphakia (ak) mouse.
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Stem cell-based cell replacement of lost midbrain dopamine (mDA) neurons is a potential therapy for Parkinson's disease (PD). Toward this goal, it is critical to optimize various aspects of cell transplantation and to assess functional recovery through behavioral tests in validated animal model(s)
In-vitro analysis of Pitx3 in mesodiencephalic dopaminergic neuron maturation.
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The transcription factor Pitx3 is expressed exclusively by mesodiencephalic dopaminergic neurons; however, ablation of Pitx3 results in selective degeneration of primarily dopaminergic neurons of the substantia nigra pars compacta, the neuronal population that is most vulnerable in Parkinson's
L-DOPA-induced increase in TH-immunoreactive striatal neurons in parkinsonian mice: insights into regulation and function.
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Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons have been found in the striatum after dopamine depletion; however, little is known about the mechanism underlying their appearance or their functional significance. We previously showed an increase in striatal TH-ir neurons after L-DOPA treatment
Dopamine regulates spine density in striatal projection neurons in a concentration-dependent manner.
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Dopaminergic afferents innervate spiny projection neurons (SPNs) in the striatum, maintaining basal ganglia activity. The loss of striatal innervation is the hallmark of Parkinson's disease (PD), which is characterized by dopaminergic denervation. A lack of dopamine in the dorsal striatum induces
Early developmental failure of substantia nigra dopamine neurons in mice lacking the homeodomain gene Pitx3.
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The mesencephalic dopamine (mesDA) system is involved in the control of movement and behavior. The expression of Pitx3 in the brain is restricted to the mesDA system and the gene is induced relatively late, at E11.5, a time when tyrosine hydroxylase (Th) gene expression is initiated. We show here
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