Fig. 11.

Model of a gene regulatory network. Our results lead us to postulate a GRN that controls the development of melanophores with Dct expression and xanthophores/leucophores with Gch2 expression. In medaka NCCs, Sox10 (Sox10a and Sox10b in medaka) and Pax3 (Pax3b in medaka) activate Mitf (Mitfa and possibly Mitfb) expression. Mitf can drive transcription of Dct and Gch2. Pax7 represses transcription of Dct by inhibiting Mitf, and promotes transcription of Gch2 cooperatively with Mitf. Pax7 may compensate for loss of Pax3 by activating Mitf expression (dotted line). Expression of Mitf and Pax7 are dependent upon promelanogenic and proxanthogenic/proleucogenic signals, respectively (the cell resides in a tripotent environment). A fraction of the Mitf-expressing cells, if expressing Pax7a (lower cell), would differentiate into the Gch2-expressing xanthophore/leucophore lineage because Mitf and Pax7 cooperatively activate Gch2 expression, whereas Pax7 represses Dct by inhibiting Mitf. Another cell, not expressing Pax7 (upper cell), would differentiate into the Dct-expressing melanophore lineage where Mitf activates Dct expression. Leu, leucophore; Mel, melanophore; Xan, xanthophore.