Zebrafish diencephalic A11-related dopaminergic neurons share a conserved transcriptional network with neuroendocrine cell lineages.

Vertebrate dopaminergic neurons develop in distinct neural territories to constitute one of the major neuromodulatory systems. We have identified a zebrafish mutation in the bHLH-PAS family member arnt2, based on a strong reduction in cell number of specific dopaminergic neuron groups in the hypothalamus and posterior tuberculum. Knockdown of sim1 causes a dopaminergic phenotype similar to arnt2 mutants, suggesting that Sim1 acts as a binding partner of Arnt2, similar to their role in hypothalamic neuroendocrine cell specification. sim1, arnt2 and otp are co-expressed in dopaminergic neurons, and combined overexpression of Sim1 and Otp leads to formation of supernumerary dopaminergic neurons in the ventral diencephalon. Arnt2, Sim1 and Otp thus are core components of a conserved transcriptional network, which specifies neuroendocrine as well as A11-related dopaminergic neurons in the fish hypothalamus and posterior tuberculum. Our data suggest a common evolutionary origin of specific hypothalamic neuroendocrine and dopaminergic systems.