Neurogenin1 is a determinant of zebrafish basal forebrain dopaminergic neurons and is regulated by the conserved zinc finger protein Tof/Fezl.
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.
Department of Biopharmaceutical Sciences, Program in Human Genetics, University of California, San Francisco, CA 94143, USA.
Jae-Yeon
JY
Jeong
Zev
Z
Einhorn
Sara
S
Mercurio
Susie
S
Lee
Billy
B
Lau
Marina
M
Mione
Stephen W
SW
Wilson
Su
S
Guo
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D048430:Cell Shape; D017124:Conserved Sequence; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D004475:Ectoderm / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
D051792:Basic Helix-Loop-Helix Proteins; D002352:Carrier Proteins; D004298:Dopamine; D009419:Nerve Tissue Proteins; D014446:Tyrosine 3-Monooxygenase; D029961:Zebrafish Proteins; C418489:fezf2 protein, zebrafish; C486337:neurog1 protein, zebrafish