Francis-West P H, Robertson K E, Ede D A, Rodriguez C, Izpisúa-Belmonte J C, Houston B, Burt D W, Gribbin C, Brickell P M, Tickle C
Department of Anatomy and Developmental Biology, University College of London, United Kingdom.
Dev Dyn. 1995 Jun;203(2):187-97. doi: 10.1002/aja.1002030207.
The chicken mutant talpid3 (ta3) has polydactylous limbs with up to 7-8 morphologically similar digits. This lack of antero-posterior polarity in digit pattern is correlated with symmetrical expression of genes of the HoxD complex. We determined the distribution of polarizing activity in limb buds of the chick mutant ta3 by assessing the ability of mesenchyme from various positions along the antero-posterior axis to induce digit duplications when grafted anteriorly into a normal limb. Cells with highest polarizing activity were found at the posterior margin of the wing as in the polarizing region of normal limb buds. However, in contrast to normal limb buds, ta3 anterior mesenchyme also had low polarizing activity. Application of retinoic acid or a polarizing region graft to the anterior of ta3 limb buds changed digit morphology but did not induce digit duplications or digits with any characteristic a-p pattern. To determine which genes are associated with polarizing activity and which are associated with patterning of the digits, we examined expression of the genes Sonic hedgehog (shh), Bmp-2, and Bmp-7, whose expression is normally confined to the posterior margin of the early wing bud and is associated with the polarizing region. In addition, we determined the distribution of Fgf-4 transcripts which in normal limb buds are restricted to the posterior part of the apical ectodermal ridge. In ta3 limb buds, shh expression is restricted to the posterior limb mesenchyme, which has high polarizing activity, but is not expressed in regions which have low polarizing activity. In contrast, Bmp-2 and Bmp-7 are expressed uniformly along the a-p axis. Fgf-4 transcripts are present throughout the apical ectodermal ridge in ta3 limb buds. In the ta3 mutant, there is both an abnormal distribution of signalling activity and response to polarizing signals. In addition, the dissociation between the expression of shh and Bmps suggests distinct roles for the encoded molecules in signalling and response in a-p patterning of limb buds.
鸡的突变体talpid3（ta3）具有多趾肢体，最多有7 - 8个形态相似的趾。趾模式中前后极性的缺失与HoxD复合体基因的对称表达相关。我们通过评估沿前后轴不同位置的间充质向前移植到正常肢体时诱导趾重复的能力，来确定鸡突变体ta3肢体芽中极化活性的分布。与正常肢体芽的极化区域一样，在翅的后缘发现了具有最高极化活性的细胞。然而，与正常肢体芽不同的是，ta3前侧间充质也具有低极化活性。将视黄酸或极化区域移植到ta3肢体芽的前部会改变趾的形态，但不会诱导趾重复或形成具有任何特征性前后模式的趾。为了确定哪些基因与极化活性相关，哪些基因与趾的模式形成相关，我们检测了音猬因子（shh）、骨形态发生蛋白-2（Bmp - 2）和骨形态发生蛋白-7（Bmp - 7）的基因表达，它们的表达通常局限于早期翅芽的后缘并与极化区域相关。此外，我们确定了成纤维细胞生长因子-4（Fgf - 4）转录本的分布，在正常肢体芽中，Fgf - 4转录本局限于顶端外胚层嵴的后部。在ta3肢体芽中，shh表达局限于具有高极化活性的后肢间充质，但在具有低极化活性的区域不表达。相反，Bmp - 2和Bmp - 7沿前后轴均匀表达。Fgf - 4转录本在ta3肢体芽的整个顶端外胚层嵴中都存在。在ta3突变体中，信号活性的分布和对极化信号的反应均异常。此外，shh和Bmps表达之间的分离表明编码分子在肢体芽前后模式形成的信号传导和反应中具有不同的作用。
