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A Key Role for Poly(ADP-ribose) Polymerase 3 in Ectodermal Specification and Neural Crest Development

Overview
Journal PLoS One
Date 2011 Jan 26
PMID 21264220
Citations 14
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Abstract

Background: The PARP family member poly(ADP-ribose) polymerase 3 (PARP3) is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose). In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.

Principal Findings: We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG) proteins. We demonstrate that PARP3 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.

Citing Articles

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Parp3 promotes astrocytic differentiation through a tight regulation of Nox4-induced ROS and mTorc2 activation.

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PARP3 comes to light as a prime target in cancer therapy.

Rodriguez-Vargas J, Nguekeu-Zebaze L, Dantzer F Cell Cycle. 2019; 18(12):1295-1301.

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Prenatal retinoic acid exposure reveals candidate genes for craniofacial disorders.

Berenguer M, Darnaudery M, Claverol S, Bonneu M, Lacombe D, Rooryck C Sci Rep. 2018; 8(1):17492.

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