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The neural crest (NC) is a transient embryonic cell population that diversifes into a wide variety of cell types including glia and neurons of the peripheral neurvous system, pigment cells and elements of the craniofacial skeleton. However, the mechanisms regulating the process of neural crest cell diversification (NCCD) are incompletely understood. A number of transcription factors as well as histone modification enzymes have been implicated in the NCCD process. Among them, zebrafish hdac1, foxd3 and tfap2a are necessary for the specification and development of neural crest sublineages. In our study, we have shown that hdac1 is required for the differentiation of enteric, DRG and sympathetic neurons. Further, in hdac1b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer posterior branchial arch precursors are specified. Second, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to differentiate. Using the HDAC inhibitor trichostatinA (TSA), we phenocopied multiple aspects of hdac1b382 mutants and defined temporal requirements of hdac1 during craniofacial and peripheral neuron development. We also uncovered a synergistic genetic interaction between tfap2a and hdac1 that is required for the specification and survival of all posterior trunk neural crest cells. We observed additive effects in cranial and trunk neural crest development in hadc1b382;tfap2alow double mutant embryos. tfap2a and hdac1 are not required for the induction of trunk neural crest cells, but they are required for posterior trunk sox10 expression. Loss of posterior trunk sox10 expression effects the specification of melanophores and DRG neurons and subsequently trunk neural crest cells undergo apoptotic cell death. Misexpression of sox10 is sufficient to rescue melanophores indicating that the genetic interaction between tfap2a and hdac1 is epistatic to sox10 function in trunk neural crest cells. Zebrafish foxd3zdf10;tfap2alow double mutant embryos completely lack all neural crest derivatives. While the induction of the neural crest is normal in these embryos, all major neural crest sublineages fail to be specified. Previous studies indicated that additional regulators of sublineage specification, dependent on foxd3 and tfap2a function, are required for the specification of these sublineages. In order to identify additional regulators of NC development, we performed expression profiling at three developmental stages using foxd3zdf10 and tfap2alow single mutants and foxd3zdf10;tfap2alow double mutants. We identified candidate genes regulated by foxd3 and/or tfap2a during different stages of NC development.