Development of noradrenergic neurons in the zebrafish hindbrain requires BMP, FGF8, and the homeodomain protein soulless/Phox2a

We report that the zebrafish mutation soulless, in which the development of locus coeruleus (LC) noradrenergic (NA) neurons failed to occur, disrupts the homeodomain protein Phox2a. Phox2a is not only necessary but also suffi cient to induce Phox2b(+) dopamine-beta-hydroxylase(+) and tyrosine hydroxy lase(+) NA neurons in ectopic locations. Phox2a is first detected in LC pro genitors in the dorsal anterior hindbrain, and its expression there is depe ndent on FGF8 from the mid/hindbrain boundary and on optimal concentrations of BMP signal from the epidermal ectoderm/future dorsal neural plate junct ion. These findings suggest that Phox2a coordinates the specification of LC in part through the induction of Phox2b and in response to cooperating sig nals that operate along the mediolateral and anteroposterior axes of the ne ural plate.