Mutations in the zebrafish unmask shared regulatory pathways controlling the development of catecholaminergic neurons

The mechanism by which pluripotent progenitors give rise to distinct classe s of mature neurons in vertebrates is not well understood. To address this issue we undertook a genetic screen for mutations which affect the commitme nt and differentiation of catecholaminergic (CA) [dopaminergic (DA), noradr energic (NA), and adrenergic] neurons in the zebrafish, Danio rerio. The id entified mutations constitute five complementation groups, motionless and f oggy affect the number and differentiation state of hypothalamic DA, telenc ephalic DA, retinal DA, locus coeruleus (LC) NA, and sympathetic NA neurons . The too few mutation leads to a specific reduction in the number of hypot halamic DA neurons, no soul lacks arch-associated NA cells and has defects in pharyngeal arches, and soulless lacks both arch-associated and LC cell g roups. Our analyses suggest that the genes defined by these mutations regul ate different steps in the differentiation of multipotent CA. progenitors. They further reveal an underlying universal mechanism for the control of CA cell fates, which involve combinatorial usage of regulatory genes. (C) 199 9 Academic Press.