Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish

斑马鱼 MEK抑制剂 MAPK/ERK通路 生物 原肠化 表型 水痘综合征 激酶 突变 癌症研究 细胞生物学 遗传学 胚胎 胚胎发生 基因 克拉斯
作者
Corina Anastasaki,Katherine A. Rauen,E. Elizabeth Patton
出处
期刊:Disease Models & Mechanisms [The Company of Biologists]
被引量:53
标识
DOI:10.1242/dmm.008672
摘要

Summary Cardio-facio-cutaneous (CFC) syndrome is caused by germ-line mutations in RAS, BRAF and MEK. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a one-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK dependent tissues. We now test 10 different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development, and craniofacial structures in zebrafish embryos. Notably, we find that a continuous, partial dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAFQ257R kinase-active allele and the BRAFG596V kinase-impaired mutant allele through the first five days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer that requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK activity treatment is sufficient to moderate the developmental effects BRAFCFC mutations.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
hollow发布了新的文献求助10
刚刚
1秒前
ding应助八角采纳,获得10
2秒前
3秒前
thth发布了新的文献求助10
3秒前
3秒前
月屿发布了新的文献求助10
4秒前
星辰大海应助璐璐采纳,获得10
4秒前
6秒前
6秒前
6秒前
情怀应助joey106采纳,获得10
8秒前
suhana发布了新的文献求助10
8秒前
李福喜完成签到,获得积分10
9秒前
9秒前
一一发布了新的文献求助20
10秒前
科研通AI6.2应助几两采纳,获得10
10秒前
12秒前
12秒前
hehehe发布了新的文献求助10
13秒前
讨厌下雨天完成签到 ,获得积分10
13秒前
充电宝应助hhhee采纳,获得10
13秒前
13秒前
梦华发布了新的文献求助10
13秒前
今后应助默默采纳,获得10
14秒前
JamesPei应助安详的方盒采纳,获得10
14秒前
老福贵儿应助踏实的老四采纳,获得10
16秒前
埃塞克斯应助yyyyy采纳,获得10
16秒前
17秒前
17秒前
yerong发布了新的文献求助10
18秒前
20秒前
传奇3应助冬瓜采纳,获得10
20秒前
木鱼发布了新的文献求助10
21秒前
21秒前
22秒前
呆萌初南发布了新的文献求助10
22秒前
璃茉完成签到,获得积分10
22秒前
SYSUer发布了新的文献求助10
22秒前
sikaixue完成签到,获得积分10
23秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Handbook of pharmaceutical excipients, Ninth edition 5000
Aerospace Standards Index - 2026 ASIN2026 3000
Digital Twins of Advanced Materials Processing 2000
Polymorphism and polytypism in crystals 1000
Signals, Systems, and Signal Processing 610
Discrete-Time Signals and Systems 610
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 纳米技术 有机化学 物理 生物化学 化学工程 计算机科学 复合材料 内科学 催化作用 光电子学 物理化学 电极 冶金 遗传学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 6039868
求助须知:如何正确求助?哪些是违规求助? 7771992
关于积分的说明 16228343
捐赠科研通 5185866
什么是DOI,文献DOI怎么找? 2775119
邀请新用户注册赠送积分活动 1758053
关于科研通互助平台的介绍 1641994