Mitf functions as an in ovo regulator for cell differentiation and proliferation during development of the chick RPE

Nagaharu Tsukiji, Daisuke Nishihara, Ichiro Yajima, Kazuhisa Takeda, Shigeki Shibahara, Hiroaki Yamamoto

研究成果: Article

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Mitf has been reported to play a crucial role in regulating the differentiation of pigment cells in homeothermal animals, i.e. the melanocytes and the retinal pigment epithelium (RPE). However, less is known about the functions of Mitf in the developing RPE. To elucidate such functions, we introduced wild-type and dominant-negative Mitf expression vectors into chick optic vesicles by electroporation. Over-expression of wild-type Mitf altered neural retina cells to become RPE-like and repressed the expression of neural retina markers in vivo. In contrast, dominant-negative Mitf inhibited pigmentation in the RPE. The percentage of BrdU-positive cells decreased during normal RPE development, which was followed by Mitf protein expression. The percentage of BrdU-positive cells decreased in the wild-type Mitf-transfected neural retina, but increased in the dominant-negative Mitf-transfected RPE. p27kip1, one of the cyclin-dependent kinase inhibitors, begins to be expressed in the proximal region of the RPE at stage 16. Transfection of wild-type Mitf induced expression of p27kip1, while transfection of dominant-negative Mitf inhibited p27kip1 expression. We found that Mitf was associated with the endogenous p27kip1 5′ flanking region. These results demonstrate for the first time "in vivo" that Mitf uniquely regulates both differentiation and cell proliferation in the developing RPE.

元の言語English
ページ(範囲)335-346
ページ数12
ジャーナルDevelopmental Biology
326
発行部数2
DOI
出版物ステータスPublished - 2009 2 15

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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