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Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development.
PLoS Genet 2014; 10(1):e1004074PG

Abstract

During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.

Authors+Show Affiliations

Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America ; Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, China.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America.Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts, United States of America.Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America.Department of Genetics, Yale School of Medicine, New Haven, Connecticut, United States of America ; Departments of Molecular Biophysics & Biochemistry and Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut, United States of America.Department of Oral and Maxillofacial Pathology, Division of Craniofacial and Molecular Genetics, Tufts University, Boston, Massachusetts, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24497835

Citation

Zhao, Chengtian, et al. "Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development." PLoS Genetics, vol. 10, no. 1, 2014, pp. e1004074.
Zhao C, Andreeva V, Gibert Y, et al. Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development. PLoS Genet. 2014;10(1):e1004074.
Zhao, C., Andreeva, V., Gibert, Y., LaBonty, M., Lattanzi, V., Prabhudesai, S., ... Yelick, P. C. (2014). Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development. PLoS Genetics, 10(1), pp. e1004074. doi:10.1371/journal.pgen.1004074.
Zhao C, et al. Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development. PLoS Genet. 2014;10(1):e1004074. PubMed PMID: 24497835.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue specific roles for the ribosome biogenesis factor Wdr43 in zebrafish development. AU - Zhao,Chengtian, AU - Andreeva,Viktoria, AU - Gibert,Yann, AU - LaBonty,Melissa, AU - Lattanzi,Victoria, AU - Prabhudesai,Shubhangi, AU - Zhou,Yi, AU - Zon,Leonard, AU - McCann,Kathleen L, AU - Baserga,Susan, AU - Yelick,Pamela C, Y1 - 2014/01/30/ PY - 2013/03/06/received PY - 2013/11/15/accepted PY - 2014/2/6/entrez PY - 2014/2/6/pubmed PY - 2014/6/18/medline SP - e1004074 EP - e1004074 JF - PLoS genetics JO - PLoS Genet. VL - 10 IS - 1 N2 - During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed ribosome biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking ribosome biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in ribosome biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, ribosome biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome. SN - 1553-7404 UR - https://www.unboundmedicine.com/medline/citation/24497835/Tissue_specific_roles_for_the_ribosome_biogenesis_factor_Wdr43_in_zebrafish_development_ L2 - http://dx.plos.org/10.1371/journal.pgen.1004074 DB - PRIME DP - Unbound Medicine ER -