Pitx1 determines characteristic hindlimb morphologies in cartilage micromass culture.
Pitx1 determines characteristic hindlimb morphologies in cartilage micromass culture.
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DOI：
10.1371/journal.pone.0180453
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Logan MPO
中科院分区：
文献类型：
--
作者：
Butterfield NC;Qian C;Logan MPO
脊椎动物前肢和后肢的同源骨骼元件的形状是不同的，每个元件都巧妙地适应了它们不同的功能。许多负责形成肢芽发育模式的信号和信号传导途径对于前肢和后肢都是常见的。在肢体发育过程中，如何从常见的信号输入产生不同的形态仍然知之甚少。我们发现，与小鸡中的情况类似，当软骨形成远离内源性肢芽环境在体外进行时，小鼠前肢和后肢软骨形态的特征差异得以维持。在源自前肢和后肢芽的高密度微团培养物中形成的软骨结节的大小和形状始终不同。我们描述了我们开发的分析工具来量化结节形态的这些差异，并证明在缺乏后肢限制性肢体修饰基因 Pitx1 的情况下，特征性后肢结节形态会丢失。此外，我们发现前肢 Pitx1 的异位表达足以产生后肢特征的结节模式。我们还证明后肢细胞对组织培养基质以及在肢体环境中与细胞外基质和彼此之间的粘附性较低。这些结果揭示了肢体骨骼的前肢和后肢软骨前体的自主编程差异至少部分地由 Pitx1 控制，并表明这在产生不同的肢体类型形态方面具有重要作用。我们的结果表明，微团培养系统非常适合在反映体内潜力的简单且实验上易于处理的体外系统中研究控制肢体骨骼元件形态发生的线索。
The shapes of homologous skeletal elements in the vertebrate forelimb and hindlimb are distinct, with each element exquisitely adapted to their divergent functions. Many of the signals and signalling pathways responsible for patterning the developing limb bud are common to both forelimb and hindlimb. How disparate morphologies are generated from common signalling inputs during limb development remains poorly understood. We show that, similar to what has been shown in the chick, characteristic differences in mouse forelimb and hindlimb cartilage morphology are maintained when chondrogenesis proceeds in vitro away from the endogenous limb bud environment. Chondrogenic nodules that form in high-density micromass cultures derived from forelimb and hindlimb buds are consistently different in size and shape. We described analytical tools we have developed to quantify these differences in nodule morphology and demonstrate that characteristic hindlimb nodule morphology is lost in the absence of the hindlimb-restricted limb modifier gene Pitx1. Furthermore, we show that ectopic expression of Pitx1 in the forelimb is sufficient to generate nodule patterns characteristic of the hindlimb. We also demonstrate that hindlimb cells are less adhesive to the tissue culture substrate and, within the limb environment, to the extracellular matrix and to each other. These results reveal autonomously programmed differences in forelimb and hindlimb cartilage precursors of the limb skeleton are controlled, at least in part, by Pitx1 and suggest this has an important role in generating distinct limb-type morphologies. Our results demonstrate that the micromass culture system is ideally suited to study cues governing morphogenesis of limb skeletal elements in a simple and experimentally tractable in vitro system that reflects in vivo potential.
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影响因子：
2.7
作者：
COTTRILL, CP;ARCHER, CW;WOLPERT, L
通讯作者：
WOLPERT, L
影响因子：
7.8
作者：
CHIQUET, M;FAMBROUGH, DM
通讯作者：
FAMBROUGH, DM
DOI：
10.1128/aem.26.2.185-190.1973
发表时间：
1973-01-01
期刊：
APPLIED MICROBIOLOGY
影响因子：
--
作者：
FOGARTY, WM;GRIFFIN, PJ
通讯作者：
GRIFFIN, PJ
影响因子：
6.9
作者：
de Crombrugghe, B;Lefebvre, V;Huang, WD
通讯作者：
Huang, WD
影响因子：
11.8
作者：
Blitz, Einat;Viukov, Sergey;Sharir, Amnon;Shwartz, Yulia;Galloway, Jenna L.;Pryce, Brian A.;Johnson, Randy L.;Tabin, Clifford J.;Schweitzer, Ronen;Zelzer, Elazar
通讯作者：
Zelzer, Elazar