Differential expression of tyrosine hydroxylase in catecholaminergic neurons of neonatal wild-type and Nurr1-deficient mice

The orphan nuclear receptor Nurr1 is a transcription factor that belongs to the steroid/thyroid hormone receptor superfamily and is expressed in many regions of the brain. To determine the physiological role of Nurr1, we prev iously generated mice with a null mutation in the Nurr1 gene. Nurr1-null mi ce appear to develop normally but die within 12 h after birth. Subsequent a nalysis revealed the absence of neurotransmitter dopamine and tyrosine hydr oxylase immunoreactivity in the central dopaminergic area of newborn pups. Herein, using in situ hybridization histochemistry, we show that Nurr1 is e xpressed only in subset of catecholamine producing neurons (A2 partly, A8-A 10 and A11 catecholaminergic cell groups), and is excluded from the norepin ephrine producing neurons (A1, A2, A5-A6 catecholaminergic cell groups). Nu rr1 was not expressed in the dopamine synthesizing cell groups (A12-A16 cat echolaminergic cell groups) of the diencephalon and the olfactory bulb. As previously shown and confirmed in this study, tyrosine hydroxylase immunore activity was absent in the substantia nigra and ventral tegmental area of N urr1-deficient mice. However, the loss of Nurr1 expression in A2 and A11 do paminergic neurons did not affect their tyrosine hydroxylase immunoreactivi ty. This study begins to dissect cues necessary for understanding the complex r egulation of the catecholaminergic biosynthetic pathway with regard to loca l, chemical and developmental changes in the brain. Published by Elsevier S cience Ltd.