Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl.

Abstract

The development of vertebrate basal forebrain dopaminergic (DA) neurons requires the conserved zinc finger protein Too Few (Tof/Fezl) in zebrafish. However, how Tof/Fezl regulates the commitment and differentiation of these DA neurons is not known. Proneural genes encoding basic helix-loop-helix transcription factors regulate the development of multiple neuronal lineages, but their involvement in vertebrate DA neuron determination is unclear. Here we show that neurogenin 1 (ngn1), a vertebrate proneural gene related to the Drosophila atonal, is expressed in and required for specification of DA progenitor cells, and when overexpressed leads to supernumerary DA neurons in the forebrain of zebrafish. Overexpression of ngn1 is also sufficient to induce tyrosine hydroxylase expression in addition to the pan-neuronal marker Hu in nonneural ectoderm. We further show that Tof/Fezl is required to establish basal forebrain ngn1-expressing DA progenitor domains. These findings identify Ngn1 as a determinant of brain DA neurons and provide insights into how Tof/Fezl regulates the development of these clinically important neuronal types.