BMP antagonism protects Nodal signaling in the gastrula to promote the tissue interactions underlying mammalian forebrain and craniofacial patterning.
BMP antagonism protects Nodal signaling in the gastrula to promote the tissue interactions underlying mammalian forebrain and craniofacial patterning.
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BMP 拮抗作用可保护原肠胚中的 Nodal 信号传导，从而促进哺乳动物前脑和颅面模式下的组织相互作用。
DOI：
10.1093/hmg/ddq208
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发表时间：
2010
影响因子：
3.5
通讯作者：
Klingensmith,John
中科院分区：
文献类型：
--
作者：
Yang,Yu-Ping;Anderson,RyanM;Klingensmith,John
前脑无裂畸形（HPE）是人类最常见的前脑和颅面畸形综合征。HPE的遗传学表明，它通常源于独立基因座中突变的协同相互作用。在小鼠中，Nodal信号传导途径组分中的几种突变组合可引起HPE，但尚不清楚Nodal信号传导的适度缺陷沿着其他途径中的病变是否也可能导致此类缺陷。我们发现，HPE的结果从同时减少Nodal信号和组织者BMP（骨形态发生蛋白）拮抗剂，无论是Chordin或Noggin。这些缺陷是由于促进前脑和颅面发育的组织产量减少造成的。Nodal促进前原条中对这些组织的发育很重要的基因的表达，而BMP抑制它们的表达。这些信号通路的药理学和转基因操作表明BMP和Nodal在细胞内信号转导之前相互拮抗。体外生物化学实验表明，分泌的Bmp 2和Nodal可以形成细胞外复合物，潜在地干扰受体激活。我们的研究结果表明，前脑和内侧颅面元素的图案化需要BMP和Nodal信号之间的良好平衡，在原始条纹的发展，并提供了一个新的多基因模型HPE的潜在机制基础。
Holoprosencephaly (HPE) is the most common forebrain and craniofacial malformation syndrome in humans. The genetics of HPE suggest that it often stems from a synergistic interaction of mutations in independent loci. In mice, several combinations of mutations in Nodal signaling pathway components can give rise to HPE, but it is not clear whether modest deficits of Nodal signaling along with lesions in other pathways might also cause such defects. We find that HPE results from simultaneous reduction of Nodal signaling and an organizer BMP (bone morphogenetic protein) antagonist, either Chordin or Noggin. These defects result from reduced production of tissues that promote forebrain and craniofacial development. Nodal promotes the expression of genes in the anterior primitive streak that are important for the development of these tissues, whereas BMP inhibits their expression. Pharmacological and transgenic manipulation of these signaling pathways suggests that BMP and Nodal antagonize each other prior to intracellular signal transduction. Biochemical experimentsin vitroindicate that secreted Bmp2 and Nodal can form extracellular complexes, potentially interfering with receptor activation. Our results reveal that the patterning of forebrain and medial craniofacial elements requires a fine balance between BMP and Nodal signaling during primitive streak development, and provide a potential mechanistic basis for a new multigenic model of HPE.
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影响因子：
15.9
作者：
LILLEY, JJ;GOLDEN, J;STONE, RA
通讯作者：
STONE, RA
使用 [123I] 和 [131I] 间碘苄胍对灵长类动物肾上腺髓质进行成像：简洁的交流。
DOI：
10.1016/s0300-595x(80)80035-1
发表时间：
1981
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
D. Wieland;L. E. Brown;M. Tobes;W. Rogers;D. D. Marsh;T. Mangner;D. Swanson;W. Beierwaltes
通讯作者：
W. Beierwaltes
唾液腺积聚间[131I]碘苄基胍。
DOI：
--
发表时间：
1984
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Nakajo,M;Shapiro,B;Sisson,JC;Swanson,DP;Beierwaltes,WH
通讯作者：
Beierwaltes,WH
摄取一抑制剂对去甲肾上腺素和间碘苄胍摄取的影响。
DOI：
--
发表时间：
1985
期刊：
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
影响因子：
--
作者：
Tobes,MC;JaquesJr,S;Wieland,DM;Sisson,JC
通讯作者：
Sisson,JC
慢性肾功能衰竭中的血浆和尿儿茶酚胺及其代谢物。
影响因子：
--
作者：
R. Darwish;A. Elias;N. Vaziri;M. Pahl;D. Powers;J. Stokes
通讯作者：
J. Stokes