The zebrafish colourless gene regulates development of non-ectomesenchymalneural crest derivatives

Neural crest forms four major categories of derivatives: pigment cells, per ipheral neurons, peripheral glia, and ectomesenchymal cells. Some early neu ral crest cells generate progeny of several fates. How specific cell fates become specified is still poorly understood. Here we show that zebrafish em bryos with mutations in the colourless gene have severe defects in most cre st-derived cell types, including pigment cells, neurons and specific glia. In contrast, craniofacial skeleton and medial fin mesenchyme are normal. Th ese observations suggest that colourless has a key role in development of n on-ectomesenchymal neural crest fates, but not in development of ectomesenc hymal fates. Thus, the cls mutant phenotype reveals a segregation of ectome senchymal and non-ectomesenchymal fates during zebrafish neural crest devel opment. The combination of pigmentation and enteric nervous system defects makes colourless mutations a model for two human neurocristopathies, Waarde nburg-Shah syndrome and Hirschsprung's disease.