Craniofacial development in the talpid3 chicken mutant
Craniofacial development in the talpid3 chicken mutant
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DOI：
10.1111/j.1432-0436.2004.07207006.x
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发表时间：
2004-09-01
期刊：
影响因子：
2.9
通讯作者：
Tickle, C
中科院分区：
文献类型：
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作者：
Buxton, P;Davey, MG;Tickle, C
talpid（3）鸡突变体具有多效性表型，包括多指（趾）畸形和颅面畸形。在talpid（3）中的肢体多指畸形提示Hedgehog（Hh）信号的获得，而矛盾的是，中线面部结构的缺失提示Hh功能的丧失。在这里，我们分析了talpid（3）突变头中Shh信号的状态。我们发现，Shh表达域从talpid（3）头部（后脑、中脑、丘脑内丘脑和口膜外胚层）丢失，并且Hedgehog信号的直接靶点Ptc1、Ptc2和Gli1甚至在与主要Shh表达相关的区域也不存在。这些数据表明，talpid（3）突变导致Shh途径的缺陷性激活，此外，发育中的头部中Shh表达的组织间转导依赖于Hh途径激活。未能激活Shh通路也可以解释中脑和后脑中底板和Hnf-3 β和Netrin-1表达的缺失以及连合板中FGF-8表达的缺失。然而，talpid（3）头部基因表达的其他方面表明了错误的表达，例如端脑中维持底板样基因表达。在鳃弓和下颌，Shh的表达，参与图案和中胚层规范的基因表达的变化表明刺猬功能的获得和丧失。因此，对talpid（3）头部中基因表达的分析表明，与talpid（3）肢体中一样，一些基因的表达丢失，而另一些基因异位表达。与肢体不同，许多头部区域依赖于Hh诱导Shh表达的二级结构域，而在talpid中这种诱导的失败，以及不能激活Shh通路，解释了功能丧失的头部表型。在talpid（3）头部中的这种基因表达分析也证实并扩展了Shh信号传导的重要性以及在颅面形态发生的许多方面中Shh靶点的激活和抑制之间的平衡的知识。
The talpid(3) chicken mutant has a pleiotropic phenotype including polydactyly and craniofacial abnormalities. Limb polydactyly in talpid(3) suggests a gain of Hedgehog (Hh) signaling, whereas, paradoxically, absence of midline facial structures suggests a loss of Hh function. Here we analyze the status of Shh signaling in the talpid(3) mutant head. We show that Shh expression domains are lost from the talpid(3) head-in hindbrain, midbrain, zona limitans intrathalamica, and stomodeal ectoderm-and that direct targets of Hedgehog signaling, Ptc1, Ptc2, and Gli1, are also absent even in areas associated with primary Shh expression. These data suggest that the talpid(3) mutation leads to defective activation of the Shh pathway and, furthermore, that tissue-to-tissue transduction of Shh expression in the developing head depends on Hh pathway activation. Failure to activate the Shh pathway can also explain absence of floor plate and Hnf-3beta and Netrin-1 expression in midbrain and hindbrain and absence of Fgf-8 expression in commissural plate. Other aspects of gene expression in the talpid(3) head, however, suggest misspecification, such as maintenance of floor plate-like gene expression in telencephalon. In branchial arches and lower jaw, where Shh is expressed, changes in expression of genes involved in patterning and mesodermal specification suggest both gain and loss of Hedgehog function. Thus, analysis of gene expression in talpid(3) head shows that, as in talpid(3) limb, expression of some genes is lost, while others are ectopically expressed. Unlike the limb, many head regions depend on Hh induction of a secondary domain of Shh expression, and failure of this induction in talpid(3), together with the inability to activate the Shh pathway, explain the loss-of-function head phenotype. This gene expression analysis in the talpid(3) head also confirms and extends knowledge of the importance of Shh signaling and the balance between activation and repression of Shh targets in many aspects of craniofacial morphogenesis.