Zebrafishcolourlessencodessox10and specifies non-ectomesenchymal neural crest fates

Abstract

Waardenburg-Shah syndrome combines the reduced enteric nervous system characteristic of Hirschsprung’s disease with reduced pigment cell number, although the cell biological basis of the disease is unclear. We have analysed a zebrafish Waardenburg-Shah syndrome model. We show that the colourless gene encodes a sox10 homologue, identify sox10 lesions in mutant alleles and rescue the mutant phenotype by ectopic sox10 expression. Using iontophoretic labelling of neural crest cells, we demonstrate that colourless mutant neural crest cells form ectomesenchymal fates. By contrast, neural crest cells which in wild types form non-ectomesenchymal fates generally fail to migrate and do not overtly differentiate. These cells die by apoptosis between 35 and 45 hours post fertilisation. We provide evidence that melanophore defects in colourless mutants can be largely explained by disruption of nacre/mitf expression. We propose that all defects of affected crest derivatives are consistent with a primary role for colourless/sox10 in specification of non-ectomesenchymal crest derivatives. This suggests a novel mechanism for the aetiology of Waardenburg-Shah syndrome in which affected neural crest derivatives fail to be generated from the neural crest.

NRG1/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration

“…They did not observe any regeneration impairment in this mutant and concluded that SC are not required for regeneration 36 . This discrepancy with our results could be explained by the fact that foxd3 exhibits a large but incomplete spatiotemporal overlap with sox10 expression 47 . Moreover, the spatiotemporal distribution of the fluorescent proteins in three transgenic lineages, Tg(foxd3:GFP) , Tg(sox10:eGFP), and Tg(sox10: mRFP), shows major differences during early NC development 36 .…”

Review: The Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

“…Subsequently, one study extended these iontophoretic labelling investigations, confirming both the apparent fate-restriction of many NCCs and the small size of wild-type zebrafish NCC clones. It also characterised a partial failure of NC migration and fate specification in the zebrafish mutants of Sox10 transcription factor ( Dutton et al, 2001 ).…”

Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

“…2f ). Supporting this conclusion further, at 14 ss, the significant deregulated targets were known components of NC development or differentiation such as sox10 , sox9b , pax3a , and zic1 37 – 40 (Fig. 2b ).…”

“…Mutations in these genes also affect craniofacial development in mice and humans 44 – 48 . Moreover, enhancer bound regions showed strong enrichment for binding sites of known regulators of NCC development such as Foxo1, Sox10, and Hoxa11 37 , 42 , 49 , 50 . To assess whether the binding of Satb2 influences gene expression, we compared corresponding transcript levels between wild-type and satb2 mutants.…”