PATTERNING ACTIVITIES OF VERTEBRATE HEDGEHOG PROTEINS IN THE DEVELOPING EYE AND BRAIN
PATTERNING ACTIVITIES OF VERTEBRATE HEDGEHOG PROTEINS IN THE DEVELOPING EYE AND BRAIN
复制标题
DOI：
10.1016/s0960-9822(95)00185-0
复制
发表时间：
1995-08-01
期刊：
影响因子：
9.2
通讯作者：
BEACHY, PA
中科院分区：
文献类型：
--
作者：
EKKER, SC;UNGAR, AR;BEACHY, PA
背景：hedgehog （hh）家族分泌的信号蛋白负责多种系统的发育模式，包括神经管、四肢和躯体。在神经管中，在脊髓水平，脊椎动物基因sonic hedgehog （shh）的产物被认为具有腹侧模式影响，具有诱导底板和运动神经元的能力。结果：我们报道了斑马鱼hh基因家族新成员tiggy-winkle， hedgehog （thwhh）的分离。thh和shh都在胚胎斑马鱼神经管和大脑的腹侧中线表达，但whh的表达仅限于神经管，而shh也在脊索表达。这两种基因都在发育中的大脑中表达，包括间脑底部的一个离散区域，位于未来视柄的位置之间。利用pax-2和pax-6作为发育中的眼睛近端命运的标记，我们发现hh基因的异位表达促进了近端命运，抑制了远端命运。相比之下，近端命运在独眼眼突变胚胎中丢失，缺乏表达whh-和sh -的前脑细胞。whth和shh蛋白在体内都经历自身蛋白水解过程；与氨基末端裂解产物对应的片段足以在眼睛和大脑发育中进行与TWHH相关的所有信号活动。结论：这些发现表明，由刺猬基因家族成员编码的信号，从神经管腹侧中线发出，不仅在大脑的背-腹侧模式中发挥重要作用，而且似乎构成了发育中的眼睛近端-远端轴的早期模式活动。
Background: 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.Results: 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.Conclusions: 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.