Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development.
Downregulation of Grem1 expression in the distal limb mesoderm is a necessary precondition for phalanx development.
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DOI：
10.1002/dvdy.431
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发表时间：
2022-09
影响因子：
2.5
通讯作者：
Fallon, John F.
中科院分区：
文献类型：
--
作者：
Lancman, Joseph J.;Hasso, Sean M.;Suzuki, Takayuki;Kherdjemil, Yacine;Kmita, Marie;Ferris, Andrea;Dong, P. Duc S.;Ros, Marian A.;Fallon, John F.
趾骨是脊椎动物肢体中形成的最后骨骼元素，并且它们的身份由位于发育中的趾射线尖端的趾骨形成区（PFR）的信号调节。在这里，我们试图探索PFR活动和指骨形态发生，这定义了最远端的肢体骨骼元素，和信号与终止肢体生长之间的关系。随着Grem 1在鸡肢体远端中胚层中消失，软骨发生标记物Aggrecan在跖骨和指骨中上调。命运映射证实，亚脊中胚层细胞有助于跖骨和趾骨亚脊Grem1下调时。Grem1过表达通过抑制PFR活性特异性阻断鸡趾骨发育。PFR活性和手指发育也被破坏后，Gli3阻遏物的过度表达，导致Grem1表达在远端肢体和下调Bmpr1b。基于表达和命运定位研究，我们提出Grem1在远端肢体的下调标志着从跖骨到趾骨发育的过渡。这表明远端肢体中胚层Grem 1的下调对于指骨发育是必要的。Grem1下调允许完全的PFR活性和趾骨祖细胞对趾命运的承诺。
The phalanges are the final skeletal elements to form in the vertebrate limb and their identity is regulated by signaling at the phalanx forming region (PFR) located at the tip of the developing digit ray. Here we seek to explore the relationship between PFR activity and phalanx morphogenesis, which define the most distal limb skeletal elements, and signals associated with termination of limb outgrowth. As Grem1 is extinguished in the distal chick limb mesoderm, the chondrogenesis marker Aggrecan is up-regulated in the metatarsals and phalanges. Fate mapping confirms that subridge mesoderm cells contribute to the metatarsal and phalanges when subridge Grem1 is down-regulated. Grem1 overexpression specifically blocks chick phalanx development by inhibiting PFR activity. PFR activity and digit development is also disrupted following overexpression of a Gli3 repressor which results in Grem1 expression in the distal limb and down-regulation of Bmpr1b. Based on expression and fate mapping studies, we propose that down-regulation of Grem1 in the distal limb marks the transition from metatarsal to phalanx development. This suggests that down-regulation of Grem1 in the distal limb mesoderm is necessary for phalanx development. Grem1 down-regulation allows for full PFR activity and phalanx progenitor cell commitment to digit fate.
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影响因子：
11.8
作者：
Lopez-Rios, Javier;Speziale, Dario;Robay, Dimitri;Scotti, Martina;Osterwalder, Marco;Nusspaumer, Gretel;Galli, Antonella;Hollaender, Georg A.;Kmita, Marie;Zeller, Rolf
通讯作者：
Zeller, Rolf
影响因子：
30.8
作者：
Khokha, MK;Hsu, D;Harland, RM
通讯作者：
Harland, RM
影响因子：
30.8
作者：
HUI, CC;JOYNER, AL
通讯作者：
JOYNER, AL
影响因子：
16
作者：
Capdevila, J;Tsukui, T;Belmonte, JCI
通讯作者：
Belmonte, JCI
影响因子：
3.5
作者：
Böse, J;Grotewold, L;Rüther, U
通讯作者：
Rüther, U