Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates

Sox10, in conjunction with Wnt signalling, is required to activate and maintain mitfa transcription.

“In this lineage, Sox10, in conjunction with Wnt signalling, is required to activate and maintain mitfa transcription [13, 20, 24–26].”

In sox10 mutants, NC derivatives fail to become specified and to enter the migration pathways.

“Specifically, as was previously reported for a single time point [14], in sox10 mutants, where NC derivatives fail to become specified and to enter the migration pathways [11, 20], tfec expression is maintained in trapped late Cbls, extending to the hindbrain/trunk boundary (Fig 7A and 7B).”

Dorsally trapped progenitors continue to express sox10 upon loss of Sox10 function.

“However, it has been previously shown that dorsally trapped progenitors continue to express sox10 upon loss of Sox10 function [26], a feature predicted successfully by models A2 and A3, but not by A1.”

By 48 hpf, tfec expression is not detectable in sox10 mutant embryos.

“By 48 hpf, we could not detect tfec expression in sox10 mutant embryos (Fig 3E and 3F), consistent with apoptotic elimination of NC derivatives which fail to become specified, including progenitors for all chromatophore lineages [26].”

Models A2 and A3, but not A1, predict that dorsally trapped progenitors continue to express sox10 upon loss of Sox10 function.

“However, it has been previously shown that dorsally trapped progenitors continue to express sox10 upon loss of Sox10 function [26], a feature predicted successfully by models A2 and A3, but not by A1.”

In the sox10 mutant context, Sox10, Tfec and Ltk acquire positive values, but Mitfa and Pnp4a do not become upregulated.

“In the sox10 mutant context we asked that Sox10, Tfec and Ltk acquire positive values, as expression has been identified in trapped chromatoblasts ([9], [26] and this work), however at no point do either Mitfa or Pnp4a become upregulated.”

Premigratory NCCs in the trunk and tail go through a multipotent pigment cell progenitor phase, referred to as the Cbl phase.

“led us to propose that premigratory NCCs in the trunk and tail go through a multipotent pigment cell progenitor phase, that we refer to here as the Cbl phase (Fig 7).”

In sox10 mutants, NCCs become trapped in the Cbl state.

“In sox10 mutants, we suggest that NCCs become trapped in the Cbl state, since specification to all non-ectomesenchymal fates is blocked [9], [26], [52].”