Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin
Control of vertebrate limb outgrowth by the proximal factor Meis2 and distal antagonism of BMPs by Gremlin
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DOI：
10.1016/s1097-2765(00)80393-7
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发表时间：
1999-11-01
期刊：
影响因子：
16
通讯作者：
Belmonte, JCI
中科院分区：
文献类型：
--
作者：
Capdevila, J;Tsukui, T;Belmonte, JCI
控制脊椎动物肢体的生长和沿沿着近端-远端轴形成图案的机制还有待理解。我们表明，限制表达的同源异型盒基因Meis 2的近端地区的肢芽是必不可少的肢体发育，因为异位Meis 2严重破坏肢体生长。我们还发现了分泌因子Gremlin和BMP之间的拮抗关系，需要维持调节远端生长的Shh/FGF环。这些近端和远端因子具有协调的活性：Meis 2可以抑制远端基因，Bmps和Hoxd基因限制Meis 2表达到近端肢芽。此外，BMP和AER因子的组合足以使近端肢体细胞远端化。我们的研究结果揭示了一套新的近端-远端监管的相互作用，建立和维持的脊椎动物肢体的生长。
The mechanisms controlling growth and patterning along the proximal-distal axis of the vertebrate limb are yet to be understood. We show that restriction of expression of the homeobox gene Meis2 to proximal regions of the limb bud is essential for limb development, since ectopic Meis2 severely disrupts limb outgrowth. We also uncover an antagonistic relationship between the secreted factors Gremlin and BMPs required to maintain the Shh/FGF loop that regulates distal outgrowth. These proximal and distal factors have coordinated activities: Meis2 can repress distal genes, and Bmps and Hoxd genes restrict Meis2 expression to the proximal limb bud. Moreover, combinations of BMPs and AER factors are sufficient to distalize proximal limb cells. Our results unveil a novel set of proximal-distal regulatory interactions that establish and maintain outgrowth of the vertebrate limb.