Fate of mesencephalic AHD2-expressing dopamine progenitor cells in Nurr1 mutant mice

The orphan nuclear receptor NURR1 was previously demonstrated to be require d for the generation of mesencephalic dopamine (DA) cells. However, even in the absence of NURR1, which is normally expressed as cells become postmito tic, neuronal differentiation is induced and expression of several genes de tected in developing dopamine cells appears normal during early stages of d evelopment. These include the homeobox transcription factors engrailed and Ptx-3 as well as aldehyde dehydrogenase 2, here defined as the earliest mar ker identified in developing DA cells, expressed already in mitotic DA prog enitors. We have used the expression of these dopaminergic markers, retrogr ade axonal tracing, and apoptosis analyses to study the fate of the DA prog enitor cells in the absence of NURR1. We conclude that NURR1 plays a critic al role in the maturation, migration, striatal target area innervation, and survival of differentiating mesencephalic DA cells. (C) 1999 Academic Pres s.