Wagner M, Thaller C, Jessell T, Eichele G
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Nature. 1990 Jun 28;345(6278):819-22. doi: 10.1038/345819a0.
In many developing organisms the establishment of axial polarity and the patterning of cells depend on local signals that derive from restricted regions of the embryo. In vertebrate embryos, the origins of tissue polarity have been examined extensively in the developing limb. The anteroposterior pattern of the chick limb seems to be controlled by a morphogen, possibly retinoic acid, that is enriched in a region of the limb known as the zone of polarizing activity (ZPA). Certain tissues other than the ZPA have also shown polarizing activity experimentally in the chick limb, raising the possibility that signalling molecules involved in pattern formation in different embryonic tissues are conserved. Here we provide evidence that a similar polarizing activity is also present in a restricted region of the developing central nervous system (CNS). We show that a specialized group of neural cells termed the floor plate, but not other regions of the CNS, mimics the ZPA in respecifying the digit pattern in the developing chick limb. In addition, using an in vitro biochemical assay, we show that the floor plate can synthesize retinoic acid and 3,4-didehydroretinol, the precursor of a second morphogenetically active retinoid, 3,4-didehydroretinoic acid. These results show that the floor plate is a local source of a ZPA-like polarizing signal, possibly a retinoid, which may regulate the pattern of cell differentiation in the developing CNS.
在许多发育中的生物体中，轴极性的建立和细胞的模式形成依赖于源自胚胎特定区域的局部信号。在脊椎动物胚胎中，组织极性的起源已在发育中的肢体中得到广泛研究。鸡胚肢体的前后模式似乎受一种形态发生素控制，可能是视黄酸，它在肢体中一个称为极化活性区（ZPA）的区域富集。除ZPA外，某些组织在鸡胚肢体中也通过实验显示出极化活性，这增加了不同胚胎组织中参与模式形成的信号分子具有保守性的可能性。在这里，我们提供证据表明，类似的极化活性也存在于发育中的中枢神经系统（CNS）的一个特定区域。我们表明，一组特殊的神经细胞，即底板，但不是中枢神经系统的其他区域，在重新确定发育中的鸡胚肢体的指（趾）模式方面模拟了ZPA。此外，使用体外生化分析，我们表明底板可以合成视黄酸和3,4-二脱氢视黄醇，后者是第二种具有形态发生活性的类视黄醇3,4-二脱氢视黄酸的前体。这些结果表明，底板是一种类似ZPA的极化信号的局部来源，可能是一种类视黄醇，它可能调节发育中的中枢神经系统中的细胞分化模式。
