Intraflagellar transport protein 172 is essential for primary cilia formation and plays a vital role in patterning the mammalian brain.
Intraflagellar transport protein 172 is essential for primary cilia formation and plays a vital role in patterning the mammalian brain.
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DOI：
10.1016/j.ydbio.2008.09.019
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发表时间：
2009-01-01
影响因子：
2.7
通讯作者：
Westphal, Heiner
中科院分区：
文献类型：
--
作者：
Gorivodsky, Marat;Mukhopadhyay, Mahua;Wilsch-Braeuninger, Michaela;Phillips, Matthew;Teufel, Andreas;Kim, Changmee;Malik, Nasir;Huttner, Wieland;Westphal, Heiner
IFT172，也被称为选择性lim结构域结合蛋白（SLB），是鞭毛内转运（IFT）复合物的一个组成部分。为了评估Ift172基因的生物学作用，我们在小鼠中产生了一个功能缺失突变。由此产生的Slb突变胚胎在E12.5-13.0之间死亡，并表现出严重的颅面畸形，无法关闭颅神经管，前脑畸形，心脏水肿和大量出血。神经上皮细胞的纤毛开始生长，但轴突严重截断，不含可见的微管。形态学和分子分析显示，沿背-腹侧（DV）和前后（AP）轴的整体脑模式缺陷。我们证明Ift172基因功能是Fgf8在中脑-后脑边界的早期调控和峡部组织者的维持所必需的。此外，Ift172对于胚胎结、早期胚胎组织器的正常功能以及头部组织中心（前中胚层，AME）的形成是必需的。我们提出了一个模型，表明前脑和中脑后脑的生长和AP模式取决于Ift172在原肠胚形成时的早期功能。我们的数据表明，小鼠胚胎中节点和AME的形成和功能依赖于Ift172在纤毛形态发生和纤毛介导的信号传导中不可或缺的作用。
IFT172, also known as Selective Lim-domain Binding protein (SLB), is a component of the Intraflagellar Transport (IFT) complex. In order to evaluate the biological role of the Ift172 gene, we generated a loss-of-function mutation in the mouse. The resulting Slb mutant embryos die between E12.5–13.0, and exhibit severe cranio-facial malformations, failure to close the cranial neural tube, holoprosencephaly, heart edema and extensive hemorrhages. Cilia outgrowth in cells of the neuroepithelium is initiated but the axonemes are severely truncated and do not contain visible microtubules. Morphological and molecular analyses revealed a global brain-patterning defect along the dorsal-ventral (DV) and anterior-posterior (AP) axes. We demonstrate that Ift172 gene function is required for early regulation of Fgf8 at the midbrain-hindbrain boundary and maintenance of the isthmic organizer. In addition, Ift172 is required for proper function of the embryonic node, the early embryonic organizer and for formation of the head organizing center (the anterior mesendoderm, or AME). We propose a model suggesting that forebrain and mid-hindbrain growth and AP patterning depends on the early function of Ift172 at gastrulation. Our data suggest that the formation and function of the node and AME in the mouse embryo relies on an indispensable role of Ift172 in cilia morphogenesis and cilia-mediated signaling.
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影响因子：
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作者：
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通讯作者：
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