Signalling through phospholipase C beta 4 is not essential for midbrain dopaminergic neuron survival

The most prominent progressive neurodegenerative movement disorder, Parkinson's disease, is attributed to selective loss of dopamine neurons in the substantia nigra pars compacta, resulting in severe deficiency of dopamine. The homeodomain gene, Pitx3, is essential for proper development of midbrain dopaminergic neurons in the substantia nigra pars compacta and might be involved in midbrain dopaminergic survival pathways. The mGluR1-signaling downstream-effector phospholipase C beta 4 was identified in a suppression subtractive hybridization screen comparing wild-type and Pitx3-deficient Aphakia midbrain dopaminergic neurons. Expression pattern analysis revealed that phospholipase C beta 4 was expressed in midbrain dopaminergic neurons of the substantia nigra pars compacta and part of the ventral tegmental area, whereas expression of mGluR1α was predominantly observed in the more vulnerable midbrain dopaminergic neurons in the lateral substantia nigra pars compacta. However, clear expression of phospholipase C beta 4 in spared midbrain dopaminergic neurons of Aphakia mice located in the ventral tegmental area, indicated that induction and maintenance of phospholipase C beta 4 expression is Pitx3-independent in these neurons. Furthermore, we report here a normal distribution of midbrain dopaminergic cell bodies and axonal projection to the striatum in phospholipase C beta 4−/− mice, indicating that signaling of phospholipase C beta 4 is not essential for the survival of midbrain dopaminergic neurons.