Constitutive activation of sonic hedgehog signaling in the chicken mutant talpid2:: Shh-independent outgrowth and polarizing activity
Constitutive activation of sonic hedgehog signaling in the chicken mutant talpid2:: Shh-independent outgrowth and polarizing activity
复制标题
DOI：
10.1006/dbio.1999.9321
复制
发表时间：
1999-08-01
影响因子：
2.7
通讯作者：
Fallon, JF
中科院分区：
文献类型：
--
作者：
Caruccio, NC;Martinez-Lopez, A;Fallon, JF
我们研究了多指鸡突变体 talpid(2) 的发育特性。尽管 Shh 表达正常，但 Ptc、Gli1、Bmp2、Hoxd13 和 Fgf4 在突变肢芽的整个前后轴上表达。 Gli3、Ihh 和 Dhh 的表达似乎正常，表明 Shh 信号通路在 talpid(2) 突变体中持续活跃。我们发现，轴前 talpid(2) 肢芽中胚层在没有可检测到的 Shh mRNA 的情况下具有极化活性。当轴后 talpid(2) 肢芽（包括所有表达 Shh 的细胞）被去除时，轴前细胞会重新形成正常形状的 talpid(2) 肢芽（调节）。然而，Shh 表达区域（极化活动区域）不会重组；然而，顶端外胚层嵴中的 Fgf4 表达得以维持。这种改造后的 talpid(2) 肢芽发育成完整的 talpid(2) 肢。经过类似的处理后，正常肢芽下调 Fgf4，轴前细胞不调节，形成截短的前后缺陷肢体。在 talpid(2) 四肢中，远端生长独立于 Shh，并与顶端外胚层嵴表达的 Fgf4 相关，但与 Fgf8 无关。我们提出了 talpid(2) 模型，其中在不存在 Shh 配体的情况下发生 Shh 信号通路的泄漏激活。 (C) 1999 年学术出版社。
We have examined the developmental properties of the polydactylous chicken mutant, talpid(2). Ptc, Gli1, Bmp2, Hoxd13, and Fgf4 are expressed throughout the anteroposterior axis of the mutant limb bud, despite normal Shh expression. The expression of Gli3, Ihh, and Dhh appears to be normal, suggesting that the Shh signaling pathway is constitutively active in talpid(2) mutants. We show that preaxial talpid(2) limb bud mesoderm has polarizing activity in the absence of detectable Shh mRNA. When the postaxial talpid(2) limb bud (including all Shh-expressing cells) is removed, the preaxial cells reform a normal-shaped talpid(2) limb bud (regulate). However, a Shh-expressing region (zone of polarizing activity) does not reform; nevertheless Fgf4 expression in the apical ectodermal ridge is maintained. Such reformed talpid(2) limb buds develop complete talpid(2) limbs. After similar treatment, normal limb buds downregulate Fgf4, the preaxial cells do not regulate, and a truncated anteroposterior deficient limb forms. In talpid(2) limbs, distal outgrowth is independent of Shh and correlates with Fgf4, but not Fgf8, expression by the apical ectodermal ridge. We propose a model for talpid(2) in which leaky activation of the Shh signaling pathway occurs in the absence of Shh ligand. (C) 1999 Academic Press.