Craniofacial and skeletal mutations are the most common human birth defects, but little is known about their aetiology. Melville et al. show that the zebrafish feelgood mutation, which causes severe skeletal malformation, is a partial loss-of-function allele of the transcription factor Creb3l2. feelgood mutant fish have selective defects in protein secretion, as Creb3l2 regulates a subset of secretory pathway proteins. The data underline the importance of intracellular transport in skeletal morphogenesis, and provide proof of principle that this link can be probed in the zebrafish model. Page 763
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