Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal; Regenerative Medicine Program, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 8005-139 Faro, Portugal; IBB-Institute for Biotechnology and Bioengineering, Centro de Biomedicina Molecular e Estrutural, Universidade do Algarve, 8005-139 Faro, Portugal.
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, 4710-057 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
J Mol Biol. 2014 Feb 20;426(4):780-4. doi: 10.1016/j.jmb.2013.11.022. Epub 2013 Dec 4.
The developing forelimb is patterned along the proximal-distal and anterior-posterior axes by opposing gradients of retinoic acid and fibroblast growth factors and by graded sonic hedgehog signaling, respectively. However, how coordinated patterning along both axes is accomplished with temporal precision remains unknown. The limb molecular oscillator hairy2 was recently shown to be a direct readout of the combined signaling activities of retinoic acid, fibroblast growth factor and sonic hedgehog in the limb mesenchyme. Herein, an integrated time-space model is presented to conciliate the progress zone and two-signal models for limb patterning. We propose that the limb clock may allow temporal information to be decoded into positional information when the distance between opposing signaling gradients is no longer sufficient to provide distinct cell fate specification.
肢体的发育是沿着近-远轴和前-后轴进行的，分别受到视黄酸和纤维生长因子的反向梯度以及分级的 sonic hedgehog 信号的影响。然而，如何在时间上精确地协调两个轴的模式形成仍然未知。肢体分子振荡器 hairy2 最近被证明是肢体间质中视黄酸、纤维生长因子和 sonic hedgehog 联合信号活性的直接读出器。在此，提出了一个集成的时空模型来调和进展区和双信号模型的肢体模式形成。我们提出，当相反信号梯度之间的距离不再足以提供明确的细胞命运指定时，肢体时钟可能允许将时间信息解码为位置信息。
