Ekker S C, Ungar A R, Greenstein P, von Kessler D P, Porter J A, Moon R T, Beachy P A
Johns Hopkins University School of Medicine, Department of Molecular Biology and Genetics, Baltimore, Maryland 21205, USA.
Curr Biol. 1995 Aug 1;5(8):944-55. doi: 10.1016/s0960-9822(95)00185-0.
The hedgehog (hh) family of secreted signaling proteins is responsible for developmental patterning in a variety of systems, including the neural tube, limbs and somites. Within the neural tube, at the level of the spinal cord, products of the vertebrate gene sonic hedgehog (shh) are proposed to function as a ventral patterning influence, with the capability of inducing floor plate and motor neurons.
We report the isolation of tiggy-winkle hedgehog (twhh), a novel member of the zebrafish hh gene family. Both twhh and shh are expressed in the ventral midline of the embryonic zebrafish neural tube and brain, but twhh expression becomes limited to the neural tube, whereas shh is also expressed in the notochord. Both genes are expressed in the developing brain, in domains that include a discrete region in the floor of the diencephalon, located between the sites of the future optic stalks. Using pax-2 and pax-6 as markers of proximo-distal fate within the developing eye, we found that ectopic expression of either hh gene promoted proximal fates and suppressed distal fates. In contrast, proximal fates were lost in cyclops mutant embryos, which lack twhh- and shh-expressing forebrain cells. Both twhh and shh proteins undergo autoproteolytic processing in vivo; a fragment corresponding to the amino-terminal cleavage product was sufficient to carry out all signaling activities associated with twhh in eye and brain development.
These findings suggest that secreted signals encoded by members of the hedgehog gene family, emanating from the ventral midline of the neural tube, not only play important roles in dorso-ventral patterning of the brain but also appear to constitute an early patterning activity along the proximo-distal axis of the developing eyes.
分泌型信号蛋白刺猬（hh）家族负责多种系统的发育模式形成，包括神经管、四肢和体节。在神经管内，在脊髓水平，脊椎动物基因音猬因子（shh）的产物被认为作为一种腹侧模式形成影响因子发挥作用，具有诱导底板和运动神经元的能力。
我们报道了斑马鱼hh基因家族的一个新成员——刺猬索尼克（twhh）的分离。twhh和shh均在斑马鱼胚胎神经管和脑的腹侧中线表达，但twhh的表达局限于神经管，而shh也在脊索中表达。这两个基因在发育中的脑中均有表达，其表达区域包括间脑底部的一个离散区域，位于未来视柄的位点之间。利用pax - 2和pax - 6作为发育中眼睛近端 - 远端命运的标记，我们发现任何一种hh基因的异位表达都促进近端命运并抑制远端命运。相比之下，独眼突变体胚胎中近端命运缺失，这些胚胎缺乏表达twhh和shh的前脑细胞。twhh和shh蛋白在体内均经历自蛋白水解加工；对应于氨基末端裂解产物的片段足以在眼睛和脑发育中执行与twhh相关的所有信号传导活性。
这些发现表明，由刺猬基因家族成员编码的分泌信号，从神经管的腹侧中线发出，不仅在脑的背 - 腹侧模式形成中发挥重要作用，而且似乎在发育中眼睛的近端 - 远端轴上构成一种早期模式形成活动。
