Is Involved in Early Cell-Fate Determination and Subset Specification of Midbrain Dopamine Neurons.

The basic helix-loop-helix (bHLH) protein family has previously been shown to be involved in the development of mesodiencephalic dopaminergic (mdDA) neurons in the murine midbrain. Specifically, and are known to have a role in the specification of neural progenitors in the ventricular zone (VZ) of the midbrain towards an mdDA neuronal cell-fate. Furthermore, other members of the bHLH protein family, the E-box factors, are expressed in the developing midbrain and are thought to have a role in neuronal differentiation. Here we show that the E-box factor is implicated in early and late development of mdDA neurons. is expressed in the midbrain and in young TH-expressing mdDA neurons throughout development. ; embryos, that lose at ~embryonic day (E)9 throughout the expression domain, have a changed spatial expression of and and a consistent loss of rostral TH expression. Expression of the subset marker is initially delayed, but recovers during development, eventually showing an ~10% increase in AHD2-expressing cells at postnatal day (P)30. ; embryos, that lose at ~E12 in post-mitotic mdDA neurons, show no effect on the amount of TH-expressing neurons in the developing midbrain. However, similar as to ; embryos, subset specification is delayed during development. Taken together, we have identified as a novel factor in mdDA neuronal development. It serves a dual function; one in early cell-fate commitment of neural progenitors and one late in subset specification.