Primary cilia regulate branching morphogenesis during mammary gland development.
Primary cilia regulate branching morphogenesis during mammary gland development.
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DOI：
10.1016/j.cub.2010.02.048
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发表时间：
2010-04-27
期刊：
影响因子：
9.2
通讯作者：
Pazour, Gregory J.
中科院分区：
文献类型：
--
作者：
McDermott, Kimberly M.;Liu, Bob Y.;Tisty, Thea D.;Pazour, Gregory J.
在乳腺发育过程中，上皮芽经历分支形态发生以扩展成分支导管的连续树状网络。该过程涉及多种细胞类型，这些细胞类型由激素和生长因子以及包括Wnt和Hedgehog在内的信号事件协调。初级纤毛通过协调细胞外信号（Wnt，Hedgehog）与细胞生理学在许多器官的发育中起关键作用。在乳腺发育过程中，我们发现纤毛腔上皮细胞，肌上皮细胞和基质细胞在早期分支形态发生时，上皮导管延伸到脂肪垫，并进行分支形态发生。当分支完成时，纤毛从腔上皮细胞消失，但保留在肌上皮细胞和基质细胞上。鞭毛内转运（IFT）缺陷引起的纤毛功能障碍导致分支缺陷。这些包括在妊娠和哺乳期间减少导管延伸和减少二级和三级分支沿着减少小叶-肺泡发育。我们发现增加的典型Wnt和减少刺猬信号在突变体腺体，这是一致的纤毛在调节这些途径的作用。在乳腺和其他器官中，增加的典型Wnt和减少的Hedgehog信号传导减少了分支形态发生，表明Wnt和Hedgehog信号传导将纤毛功能障碍与分支缺陷联系起来。
During mammary gland development an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (Wnt, Hedgehog) with cellular physiology. During mammary development, we find cilia on luminal epithelial, myoepithelial and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport (IFT) defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways. In mammary gland and other organs, increased canonical Wnt and decreased Hedgehog signaling decreases branching morphogenesis suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects.
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DOI：
10.1083/jcb.200907126
发表时间：
2009-11-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Milenkovic L;Scott MP;Rohatgi R
通讯作者：
Rohatgi R
DOI：
10.1023/b:jomg.0000037157.94207.33
发表时间：
2004-04-01
影响因子：
2.5
作者：
Brennan, KR;Brown, AMC
通讯作者：
Brown, AMC
影响因子：
9.2
作者：
Pepicelli, CV;Lewis, PM;McMahon, AP
通讯作者：
McMahon, AP
影响因子：
3.7
作者：
Ocbina PJ;Tuson M;Anderson KV
通讯作者：
Anderson KV
影响因子：
4
作者：
FIDDLER, TJ;BIRKINSHAW, M;FALCONER, IR
通讯作者：
FALCONER, IR