期刊
DEVELOPMENTAL CELL
卷 35, 期 3, 页码 322-332出版社
CELL PRESS
DOI: 10.1016/j.devcel.2015.10.006
关键词
-
资金
- NHLBI [HL113870, 119946, 122406]
- Wisconsin Partnership Program Collaborative Research Award [2900]
- American Heart predoctoral fellowship [11PRE5540006]
- NIH predoctoral training grant [T32 GM007133]
- National Institutes of Health, National Cancer Institute, and Center for Cancer Research
The mammalian lung forms its elaborate tree-like structure following a largely stereotypical branching sequence. While a number of genes have been identified to play essential roles in lung branching, what coordinates the choice between branch growth and new branch formation has not been elucidated. Here we show that loss of FGF-activated transcription factor genes, Etv4 and Etv5 (collectively Etv), led to prolonged branch tip growth and delayed new branch formation. Unexpectedly, this phenotype is more similar to mutants with increased rather than decreased FGF activity. Indeed, an increased Fgf10 expression is observed, and reducing Fgf10 dosage can attenuate the Etv mutant phenotype. Further evidence indicates that ETV inhibits Fgf10 via directly promoting Shh expression. SHH in turn inhibits local Fgf10 expression and redirects growth, thereby initiating new branches. Together, our findings establish EN as a key node in the FGF-ETV-SHH inhibitory feedback loop that dictates branching periodicity.
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