Sp8 is crucial for limb outgrowth and neuropore closure
Sp8 is crucial for limb outgrowth and neuropore closure
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DOI：
10.1073/pnas.2134310100
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发表时间：
2003-10-14
影响因子：
11.1
通讯作者：
Scott, WJ
中科院分区：
文献类型：
--
作者：
Bell, SM;Schreiner, CM;Scott, WJ
在本报告中，我们描述了锌指转录因子 Sp 家族成员 Sp8 的发育表达和功能，并提供了无腿转基因插入突变体是 Sp8 基因的亚等位基因的证据。 Sp8 在胚胎发生过程中在形成的顶外胚层脊 (AER)、中枢神经系统的限制区域和尾芽中表达。 Sp8基因的靶向缺失产生了惊人的表型，前肢和后肢严重截短，尾巴缺失，以及导致前脑畸形和脊柱裂的前部和后部神经孔闭合缺陷。肢体的生长取决于 AER 的形成，AER 是在肢芽顶端形成的信号中心。在 Sp8 突变体中，AER 前体细胞被诱导并最初表达多个适当的标记基因，但这些基因的表达无法维持，并且向成熟 AER 的进展受阻。这些观察结果表明，Sp8 在介导 AER 形成的信号级联中发挥 Wnt3、Fgf10 和 Bmpr1a 下游的作用。
In this report we describe the developmental expression and function of Sp8, a member of the Sp family of zinc finger transcription factors, and provide evidence that the legless transgene insertional mutant is a hypomorphic allele of the Sp8 gene. Sp8 is expressed during embryogenesis in the forming apical ectodermal ridge (AER), restricted regions of the central nervous system, and tail bud. Targeted deletion of the Sp8 gene gives a striking phenotype, with severe truncation of both forelimbs and hindlimbs, absent tail, as well as defects in anterior and posterior neuropore closure leading to exencephaly and Spina bifida. Outgrowth of the limb depends on formation of the AER, a signaling center that forms at the limb bud apex. In Sp8 mutants, the AER precursor cells are induced and initially express multiple appropriate marker genes, but expression of these genes is not maintained and progression to a mature AER is blocked. These observations indicate that Sp8 functions downstream of Wnt3, Fgf10, and Bmpr1a in the signaling cascade that mediates AER formation.