A key role for poly(ADP-ribose) polymerase 3 in ectodermal specification and neural crest development.

BACKGROUND:The family member poly(ADP-ribose) polymerase 3 is structurally related to the well characterized that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose). In contrast to Pduanyu371 and the functions of are undefined. Here, we reveal critical functions for Pduanyu373 during vertebrate development. PRINCIPAL FINDINGS:We have used several in vitro and in vivo approaches to examine the possible functions of Pduanyu373 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG) proteins. We demonstrate that Pduanyu373 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud. CONCLUSION:Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

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