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. 2017 Jul 19;11:215. doi: 10.3389/fncel.2017.00215

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Copyright © 2017 Spencer and Deneris.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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5-HT neuron gene regulatory network. All arrows indicate activation and diamonds indicate direct binding of the transcription factor to the promoter of the target gene as determined by ChIP experiments. 5-HT neuron generation in rhombomere 1 is driven by Foxa2 and Nkx6.1 (in chick). Ascl1 acts as a pro-neural factor activating expression of Gata2, Gata3, and Insm1 in parallel to Foxa2 and Nkx6.1. Terminal differentiation is initiated by Gata3, Lmx1b, and Pet-1 through the activation of the 5-HT neuron gene battery (Tph2, Gch1, Gchfr, Qdpr, Ddc, Slc18a2, Slc6a4, Slc22a3, Maob). Tph2, tryptophan hydroxylase 2; Gch1, GTP cyclohydrolase 1; Gchfr, GTP cyclohydrolase 1 feedback regulator; Qdpr, quinoid dihydropteridine reductase; Ddc, AADC, aromatic L-amino acid decarboxylase; Slc18a2, Vmat2, vesicular monoamine transporter 2; Slc6a4, SERT, 5-HTT, serotonin transporter; Slc22a3, Oct3, organic cation transporter 3; Maob, monoamine oxidase B.