Mouse dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling
Mouse dispatched homolog1 is required for long-range, but not juxtacrine, Hh signaling
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DOI：
10.1016/s0960-9822(02)01147-8
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发表时间：
2002-09-17
期刊：
影响因子：
9.2
通讯作者：
Anderson, KV
中科院分区：
文献类型：
--
作者：
Caspary, T;García-García, MJ;Anderson, KV
沿着脊髓背腹轴的细胞类型沿着精确的模式化对于建立功能性神经回路是必不可少的[1]。为了证明在小鼠中通过随机诱变研究单个生物过程的可行性，我们已经确定了6个基因中的隐性ENU诱导突变，这些突变阻止了脊髓中腹侧细胞类型的正常规范。我们定位克隆的基因负责两个突变表型，smoothened和派遣，这是同源的果蝇Hh通路组件。调度同源物1（Disp1）突变在妊娠中期导致致死性，并阻止神经管中腹侧细胞类型的特异性，这是一种与Smoothened（Smo）无效表型相同的表型。在果蝇中，需要小鼠Disp1将Shh从合成位点移开。尽管存在第二个小鼠disp同源物，Disp 1是必不可少的Shh和Ihh配体的远程信号。我们的数据表明，Shh信号是必需的脊索内，以保持Shh的表达，并防止脊索变性。与Smo不同，Disp 1不是Shh的这种阿曲他克林信号传导所必需的。
Precise patterning of cell types along the dorsal-ventral axis of the spinal cord is essential to establish functional neural circuits [1]. In order to prove the feasibility of studying a single biological process through random mutagenesis in the mouse, we have identified recessive ENU-induced mutations in six genes that prevent normal specification of ventral cell types in the spinal cord. We positionally cloned the genes responsible for two of the mutant phenotypes, smoothened and dispatched, which are homologs of Drosophila Hh pathway components. The Dispatched homolog1 (Disp1) mutation causes lethality at midgestation and prevents specification of ventral cell types in the neural tube, a phenotype identical to the Smoothened (Smo) null phenotype. As in Drosophila, mouse Disp1 is required to move Shh away from the site of synthesis. Despite the existence of a second mouse disp homolog, Disp1 is essential for long-range signaling by both Shh and Ihh ligands. Our data indicate that Shh signaling is required within the notochord to maintain Shh expression and to prevent notochord degeneration. Disp1, unlike Smo, is not required for this juxtacrine signaling by Shh.