The role of Zic family zinc finger transcription factors in the proliferation and differentiation of retinal progenitor cells.
Members of the Zic family of zinc finger transcription factors play critical roles in a variety of developmental processes. Using DNA microarray analysis, we found that Zics are strongly expressed in SSEA-1-positive early retinal progenitors in the peripheral region of the mouse retina. Reverse-transcription polymerase chain reaction using mRNA from the retina at various developmental stages showed that Zic1 and Zic2 are expressed in the embryonic retina and then gradually disappear during retinal development. Zic3 is also expressed in the embryonic retina; its expression level slightly decreases but it is expressed until adulthood. We overexpressed Zic1, Zic2, or Zic3 in retinal progenitors at embryonic day 17.5 and cultured the retina as explants for 2 weeks. The number of rod photoreceptors was fewer than in the control, but no other cell types showed significant differences between control and Zic overexpressing cells. The proliferation activity of normal retinal progenitors decreased after 5 days in culture, as observed in normal in vivo developmental processes. However, Zic expressing retinal cells continued to proliferate at days 5 and 7, suggesting that Zics sustain the proliferation activities of retinal progenitor cells. Since the effects of Zic1, 2, and 3 are indistinguishable in terms of differentiation and proliferation of retinal progenitors, the redundant function of Zics in retinal development is suggested.
Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Japan.
Yui
Y
Watabe
Yukihiro
Y
Baba
Hiromitsu
H
Nakauchi
Atsushi
A
Mizota
Sumiko
S
Watanabe
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D012160:Retina / Q000166:cytology / Q000254:growth & development*; D013234:Stem Cells / Q000166:cytology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018398:Homeodomain Proteins; D014157:Transcription Factors; C492122:Zic1 protein, mouse; C491811:Zic2 protein, mouse; C491594:Zic3 protein, mouse