Zhang X M, Ramalho-Santos M, McMahon A P
Department of Molecular and Cellular Biology, The Biolabs, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
Cell. 2001 Jun 15;105(6):781-92.
Genetic analyses in Drosophila have demonstrated that the multipass membrane protein Smoothened (Smo) is essential for all Hedgehog signaling. We show that Smo acts epistatic to Ptc1 to mediate Shh and Ihh signaling in the early mouse embryo. Smo and Shh/Ihh compound mutants have identical phenotypes: embryos fail to turn, arresting at somite stages with a small, linear heart tube, an open gut and cyclopia. The absence of visible left/right (L/R) asymmetry led us to examine the pathways controlling L/R situs. We present evidence consistent with a model in which Hedgehog signaling within the node is required for activation of Gdf1, and induction of left-side determinants. Further, we demonstrate an absolute requirement for Hedgehog signaling in sclerotomal development and a role in cardiac morphogenesis.[Dedicated to Rosa Beddington, a pioneer in mammalian embryology].
果蝇的遗传学分析表明，多次跨膜蛋白平滑化蛋白（Smo）对于所有刺猬索尼信号传导至关重要。我们发现，Smo在小鼠早期胚胎中介导音猬因子（Shh）和印度刺猬因子（Ihh）信号传导时，作用于patched1（Ptc1）的上位基因。Smo和Shh/Ihh复合突变体具有相同的表型：胚胎无法转动，在体节期停滞，心脏管小且呈线性，肠道开放，独眼畸形。由于缺乏明显的左右（L/R）不对称性，我们进而研究了控制L/R位的信号通路。我们提供的证据与一个模型相符，即节点内的刺猬索尼信号传导对于激活生长分化因子1（Gdf1）以及诱导左侧决定因素是必需的。此外，我们证明了在硬骨节发育中刺猬索尼信号传导的绝对必要性以及在心脏形态发生中的作用。[谨献给罗莎·贝丁顿，哺乳动物胚胎学的先驱]
