WDR55 Is a Nucleolar Modulator of Ribosomal RNA Synthesis, Cell Cycle Progression, and Teleost Organ Development

نویسندگان

  • Norimasa Iwanami
  • Tomokazu Higuchi
  • Yumi Sasano
  • Toshinobu Fujiwara
  • Vu Q. Hoa
  • Minoru Okada
  • Sadiqur R. Talukder
  • Sanae Kunimatsu
  • Jie Li
  • Fumi Saito
  • Chitralekha Bhattacharya
  • Angabin Matin
  • Takashi Sasaki
  • Nobuyoshi Shimizu
  • Hiroshi Mitani
  • Heinz Himmelbauer
  • Akihiro Momoi
  • Hisato Kondoh
  • Makoto Furutani-Seiki
  • Yousuke Takahama
چکیده

The thymus is a vertebrate-specific organ where T lymphocytes are generated. Genetic programs that lead to thymus development are incompletely understood. We previously screened ethylnitrosourea-induced medaka mutants for recessive defects in thymus development. Here we report that one of those mutants is caused by a missense mutation in a gene encoding the previously uncharacterized protein WDR55 carrying the tryptophan-aspartate-repeat motif. We find that WDR55 is a novel nucleolar protein involved in the production of ribosomal RNA (rRNA). Defects in WDR55 cause aberrant accumulation of rRNA intermediates and cell cycle arrest. A mutation in WDR55 in zebrafish also leads to analogous defects in thymus development, whereas WDR55-null mice are lethal before implantation. These results indicate that WDR55 is a nuclear modulator of rRNA synthesis, cell cycle progression, and embryonic organogenesis including teleost thymus development.

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عنوان ژورنال:
  • PLoS Genetics

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2008