| 摘要 | PEDF 蛋白（Pigment epithelium-derived factor）又名“色素上皮源因子”或
“色素上皮衍生因子”，为一个多功能性分泌糖蛋白，前人研究表明PEDF 蛋白
具有神经保护性、免疫调节、抑制新生血管生成以及抑制肿瘤恶化等多种功能。
PEDF-R 是PEDF 的受体， 属于PNPLA2 （ Patatin-like phopholipase
domain-containing 2 family）蛋白家族的一个新成员，PEDF 蛋白与其结合后会激
活PEDF-R 的磷脂酶A2 活性。本研究中，我们描述了非洲爪蟾PEDF 和PEDF-R
基因的表达图式及其在胚胎发育中的可能功能。RT-PCR 结果显示PEDF 是非母
源性表达，而PEDF-R 则是母源性表达的。原位杂交实验表明它们均在神经系统
中特异表达，但PEDF-R 的表达区域更加广泛，在鳃弓、眼泡和耳泡中也有表达。
通过mRNA 过表达和Morpholino(MO)阻断蛋白合成等手段发现，PEDF 功能获
得和功能缺失后胚胎几乎不受影响。然而PEDF-R 过表达后胚胎向注射一侧弯
曲，TUNEL 凋亡检测实验发现这些胚胎在注射一侧发生了凋亡。这两个基因神
经表达的特异性表明它们可能在早期神经发育中有重要功能。TUNEL 结果暗示
着PEDF-R 可能是一个与凋亡信号通路相关的受体。PEDF 功能获得和缺失并未
导致胚胎明显的表型，这表明PEDF 在非洲爪蟾中可能还存在其他的受体来行使
与PEDF-R 不同功能的途径。
果蝇的vestigial 基因编码一个转录辅助因子，在果蝇中只有一个成员，即
vestigial(vg)基因。在脊椎动物中有四个vestigial 同源基因，即vestigial-like 1,2,3,4_(vgl-1,2,3,4)。Vestigial 蛋白能作为辅助因子与果蝇中的Scalloped(Sd)蛋白
或者哺乳动物中的TEF 蛋白结合成复合体，通过Sd/TEF 蛋白的TEA/ATTS 结构
域与DNA 结合，从而调节下游基因的转录。本研究中，我们克隆了非洲爪蟾
vestigial-like 家族的四个成员，并对其在爪蟾胚胎发育过程中的表达进行研究。
RT-PCR 显示vgl-2 和vgl-3 是合子型表达的，vgl-1、vgl-4 则是母源性表达。原位
杂交显示：vgl-1 主要在神经管背部、耳泡和眼泡中表达；vgl-2 则是在肌肉、第
一二鳃弓、脊索中特异表达；vgl-3 神经胚时期在后脑有强的表达信号，从神经
胚后期到尾芽期后脑部位的表达几乎消失了，而在胚胎的头部以及神经管中开始
有微弱的表达；vgl-4 的表达较广泛，在神经管、眼泡、耳泡、肌肉以及脊索中
均有表达。在爪蟾中这四个成员的表达图式各不相同，提示它们有可能与其行使
组织特异性基因调控的功能相关，上述结果将有助于对vestigial-like 家族基因在
胚胎发育中的功能研究。 |
| 其他摘要 | PEDF_(Pigment epithelium-derived factor) is a secreted glycoprotein that
belongs to the non-inhibitory serpin family group. Recent studies have demonstrated
that PEDF possesses neurotropic, neuroprotective, anti-angiogenic, anti-thrombogenic,
anti-oxidative, anti-inflammatory, and insulin-sensitizing activities, and has been
considered as a good potential therapeutic candidate for the treatment of a variety of
disorders. PEDF-R is a new member of the patatin-like phospholipase domain
containing 2_(PNPLA2) family, and recently has been identified as a lipase-linked
cell membrane receptor for PEDF. In this study, we describe the expression pattern
and the possible roles of PEDF and PEDF-R genes during Xenopus development.
PEDF is not expressed until neurula stage, while its receptor PEDF-R is expressed
maternally. Whole-mount in situ hybridization showed that both of them are mainly
expressed in the nervous system, but the expression of PEDF-R is wider which could
be found in branchial arches, optic and otic vesicles. Then we analyzed the roles of
PEDF and its receptor by gain and loss of function studies in Xenopus laevis. Neither
overexpression nor knockdown of PEDF has clear phenotypic effect on Xenopus
embryos. Interestingly, overexpression of PEDF-R mRNA specifically induces
apoptosis in the injected side. These results suggest that PEDF-R maybe related to the
apoptosis pathway, and the possible existence of other PEDF receptors.
Vestigial-like family of transcription co-factor involved in the regulation of tissue-specific gene expression through binding to members of the broadly expressed
Scalloped/Tef/TEAD transcription factor family, which can bind DNA through the
TEA/ATTS domain. In Drosophila there is only a single vestigial_(vg) gene, while
there are four vg homologous genes in most vertebrates, named vestigial-like
1,2,3,4_(vgl-1,2,3,4). In this study, we have cloned these four members of
vestigial-like family genes in Xenopus laevis, and analyzed their expression pattern
during Xenopus embryonic development. Among them, vgl-1 and vgl-4 are
maternally expressed, while vgl-2 and vgl-3 start their zygotic expression from
neurula stage. vgl-1 is expressed in the dorsal neural tube , optic and otic vesicles,
while vgl-2 is specifically detected in muscle, the first two branchial arches and
notochord. vgl-3 is found only expressed in the hindbrain at the neurula stage
embryos and later it expresses weakly and ubiquitously at the nervous system. The
expression domain of vgl-4 is wider than the other three genes, which can be
detected in the nervous system, branchial arches, optic and otic vesicles, notochord
and muscles. The differential expression patterns of the vestigial-like family genes in
Xenopus suggest different roles of these factors during embryonic development. |
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