期刊
DEVELOPMENTAL BIOLOGY
卷 251, 期 2, 页码 320-332出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1006/dbio.2002.0811
关键词
GLI3; FGF8; SHH; brain patterning; optic field; limb development; facial malformation; apoptosis
The zinc finger transcription factor GLI3 is considered a repressor of vertebrate Hedgehog (Hh) signaling. In humans, the absence of GLI3 function causes Greig cephalopolysyndactyly syndrome, affecting the development of the brain, eye, face, and limb. Because the etiology of these malformations is not well understood, we examined the phenotype of mouse Gli3(-/-) mutants as a model to investigate this. We observed an up-regulation of Fgf8 in the anterior neural ridge, isthmus, eye, facial primordia, and limb buds of mutant embryos, sites coinciding with the human disease. intriguingly, endogenous apoptosis was reduced in Fgf8-positive areas in Gli3(-/-) mutants. Since SHH is thought to be involved in Fgf8 regulation, we compared Fgf8 expression in Shh(-/-) and Gli3(-/-);Shh(-/-) mutant embryos. Whereas Fgf8 expression was almost absent in Shh(-/-) mutants, it was up-regulated in Gli3(-/-);Shh(-/-) double mutants, suggesting that SHH is not required for Fgf8 induction, and that GLI3 normally represses FgfS independently of SHH In the limb bud, we provide evidence that ectopic expression of Gremlin in Gli3(-/-) mutants might contribute to a decrease in apoptosis. Together, our data reveal that GLI3 limits Fgf8-expression domains in multiple tissues, through a mechanism that may include the induction or maintenance of apoptosis. (C) 2002 Elsevier Science (USA)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据