Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head.
Inactivation of Msx1 and Msx2 in neural crest reveals an unexpected role in suppressing heterotopic bone formation in the head.
复制标题
DOI：
10.1016/j.ydbio.2010.04.007
复制
发表时间：
2010-07-01
影响因子：
2.7
通讯作者：
Maxson, Robert E.
中科院分区：
文献类型：
--
作者：
Roybal, Paul G.;Wu, Nancy L.;Sun, Jingjing;Ting, Man-chun;Schafer, Christopher A.;Maxson, Robert E.
为了理解形成头骨的形态发生力，我们在神经嵴中有条件地灭活了Msx 1和Msx 2。我们发现，Wnt 1-Cre失活多达三个Msx 1/2等位基因的结果在神经嵴衍生额骨的一个渐进的更大的缺陷。出乎意料的是，在缺乏所有四个Msx 1/2等位基因的胚胎中，大的缺陷被错误的骨骼填充，这些骨骼由减少的额骨之间的异位骨岛组成，就在顶骨之前。骨来源于神经嵴，而不是中胚层，并且，根据DiI细胞标记实验，起源于正常非成骨细胞层，通过该层，原基向顶端延伸。与异位成骨相关的是该细胞层中BMP信号的上调。通过在头部外植体中植入头蛋白浸泡的珠子来防止这种上调也防止了异位骨形成。这些结果表明，Msx基因在颅骨发育中具有双重作用：它们是雏形内成骨细胞的分化和增殖所需的，并且它们还需要抑制雏形生长的细胞层中的成骨程序。我们认为，这种抑制活性的失活可能是蠕虫骨的原因之一，异位骨是各种病理条件的特征，其中颅骨发育受到损害。
In an effort to understand the morphogenetic forces that shape the bones of the skull, we inactivated Msx1 and Msx2 conditionally in neural crest. We show that Wnt1-Cre inactivation of up to three Msx1/2 alleles results in a progressively larger defect in the neural crest-derived frontal bone. Unexpectedly, in embryos lacking all four Msx1/2 alleles, the large defect is filled in with mispatterned bone consisting of ectopic islands of bone between the reduced frontal bones, just anterior to the parietal bones. The bone is derived from neural crest, not mesoderm, and, from DiI cell marking experiments, originates in a normally non-osteogenic layer of cells through which the rudiment elongates apically. Associated with the heterotopic osteogeneis is an upregulation of Bmp signaling in this cell layer. Prevention of this upregulation by implantation of noggin-soaked beads in head explants also prevented heterotopic bone formation. These results suggest that Msx genes have a dual role in calvarial development: They are required for the differentiation and proliferation of osteogenic cells within rudiments, and they are also required to suppress an osteogenic program in a cell layer within which the rudiments grow. We suggest that the inactivation of this repressive activity may be one cause of Wormian bones, ectopic bones that are a feature of a variety of pathological conditions in which calvarial bone development is compromised.
登录
查看更多内容
影响因子：
4.8
作者：
Hu, D;Helms, J
通讯作者：
Helms, J
影响因子：
2
作者：
Sanchez-Lara, Pedro A.;Graham, John M., Jr.;Cunningham, Michael
通讯作者：
Cunningham, Michael
影响因子：
4.6
作者：
Ishii, M;Merrill, AE;Maxson, RE
通讯作者：
Maxson, RE
影响因子：
2.7
作者：
Lana-Elola, Eva;Rice, Ritva;Rice, David P. C.
通讯作者：
Rice, David P. C.
影响因子：
2.7
作者：
Jiang, XB;Iseki, S;Morriss-Kay, GM
通讯作者：
Morriss-Kay, GM