A second independent pathway for development of mesencephalic dopaminergicneurons requires Lmx1b

We identified the LIM homeodomain transcription factor Lmx1b in the mesence phalic dopamine (mesDA) systems of embryos and adults. Analysis of spatiote mporal expression in Lmx1b null mutants and wild-type mice implicated a cas cade involving Lmx1b in the early development of mesDA neurons. Although di sruption of this cascade did not block induction of tyrosine hydroxylase (T H), a key enzyme in DA synthesis, or Nurr1, a nuclear hormone receptor, Lmx 1b knockout mice failed to induce the mesDA-specific homeodomain gene Ptx3 in TH-positive neurons. Eventually, this small set of TH-positive neurons w as lost during embryonic maturation. The data suggest that at least two mol ecular cascades operate during the specification of the mesDA system, one s pecifying neurotransmitter phenotype and another essential for other aspect s of mesDA neuron differentiation.