Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity
Unique SMAD1/5/8 activity at the phalanx-forming region determines digit identity
复制标题
DOI：
10.1073/pnas.0707899105
复制
发表时间：
2008-03-18
影响因子：
11.1
通讯作者：
Fallon, John F.
中科院分区：
文献类型：
--
作者：
Suzuki, Takayuki;Hasso, Sean M.;Fallon, John F.
极化活动区是控制羊膜肢芽前后模式的主要信号中心。自动足部指间 (ID) 是次要信号中心，旨在通过作用于数字射线的细胞来确定数字身份。在这里，我们关注伴随数字命运决定的事件，并定义表达 Sox9 和 Bmpr1b 且磷酸化-SMAD1/5/8 (p-SMAD1/5/8) 阳性的数字射线区域。我们将该区域命名为指骨形成区域（PFR），并表明 PFR 细胞起源于指趾射线的远端亚脊间充质。这种指骨形成细胞谱系随后被定型为软骨谱系；这些细胞的命运最初是不稳定的，但当它们融入到手指原基的浓缩软骨中时，它们的命运就变得固定了。使用体内报告基因检测，我们确定每个数字 PFR 都具有独特的 p-SMAD1/5/8 活性特征。此外，我们还表明，这种活动的变化与实验操作后形成的数字的身份相关，这支持了阈值信号水平可以导致形态发生领域不同发育结果的观点。我们的数据定义了 PFR 的分子特征，并且我们提出了一个模型来理解自足发育过程中手指的形成和变化。
The zone of polarizing activity is the primary signaling center controlling anterior-posterior patterning of the amniote limb bud. The autopodial interdigits (IDs) are secondary signaling centers proposed to determine digit identity by acting on the cells of the digital ray. Here, we focus on events accompanying digital fate determination and define a region of the digital ray that expresses Sox9 and Bmpr1b and is phosphorylated-SMAD1/5/8 (p-SMAD1/5/8) positive. We name this region the phalanx-forming region (PFR), and show that the PFR cells arise from the distal subridge mesenchyme of digital ray. This phalanx-forming cell lineage is subsequently committed to the cartilage lineage; the fate of these cells is initially labile but becomes fixed as they are incorporated into the condensed cartilage of the digit primordium. Using an in vivo reporter assay, we establish that each digital PFR has a unique p-SMAD1/5/8 activity signature. In addition, we show that changes in this activity correlate with the identity of the digit that forms after experimental manipulation, supporting the idea that threshold signaling levels can lead to different developmental outcomes in a morphogenetic field. Our data define the molecular profile of the PFR, and we propose a model for understanding formation and variation of digits during autopodial development.