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


RESULTS
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.


CONCLUSIONS
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.
Cancer Research Laboratory, CHUQ Research Center, Centre Hospitalier de l'Université Laval, Québec, Canada.
Michèle
M
Rouleau
Vishal
V
Saxena
Amélie
A
Rodrigue
Eric R
ER
Paquet
Abbie
A
Gagnon
Michael J
MJ
Hendzel
Jean-Yves
JY
Masson
Marc
M
Ekker
Guy G
GG
Poirier
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D045744:Cell Line, Tumor; D004475:Ectoderm / Q000201:enzymology*; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D009432:Neural Crest / Q000201:enzymology* / Q000254:growth & development*; D009447:Neuroblastoma / Q000473:pathology; D055495:Neurogenesis; D010858:Pigmentation; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000502:physiology*; D055758:SOX9 Transcription Factor / Q000235:genetics; D014018:Tissue Distribution; D014157:Transcription Factors / Q000235:genetics*; D015027:Zebrafish / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
D018797:Cell Cycle Proteins; D018398:Homeodomain Proteins; D055758:SOX9 Transcription Factor; C504918:Sox9a protein, zebrafish; D014157:Transcription Factors; D029961:Zebrafish Proteins; C498152:dlx3b protein, zebrafish; C480979:PARP3 protein, human; C559916:PARP3 protein, zebrafish; D011065:Poly(ADP-ribose) Polymerases
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