Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development
Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development
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DOI：
10.1002/dvdy.20883
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发表时间：
2006-10-01
影响因子：
2.5
通讯作者：
Chang, Long-Sheng
中科院分区：
文献类型：
--
作者：
Akhmametyeva, Elena M.;Mihaylova, Maria M.;Chang, Long-Sheng
神经纤维瘤病2（NF 2）基因突变与前庭神经鞘瘤、脊髓神经鞘瘤、脑膜瘤和室管膜瘤的易感性相关。目前，NF 2如何在胚胎发育过程中和受神经纤维瘤病2型（NF 2）影响的组织中表达尚未得到很好的定义。为了研究NF 2在体内的表达，我们产生了转基因小鼠携带2.4 kb的NF 2启动子驱动β-半乳糖苷酶（β-半乳糖）与核定位信号。整装胚胎染色显示，NF 2启动子指导β-半乳糖表达早在胚胎天E5.5。在E6.5时，在含有许多有丝分裂细胞的胚胎外胚层中检测到强表达。在部分胚胎内胚层和中胚层中也发现β-半乳糖染色。内源性Nf 2 RNA表达的原位杂交分析证实了胚胎组织中的β-gal染色模式。重要的是，我们观察到强大的NF 2启动子活性在发育中的大脑和网站包含迁移细胞，包括神经管关闭，鳃弓，背主动脉，腹主动脉旁的内脏胸膜。此外，我们注意到在神经嵴细胞迁移过程中NF 2启动子活性的短暂变化。虽然很少β-半乳糖的活动被检测到在premigration神经嵴细胞的背脊区域的神经褶皱，显着的活动被认为是在神经嵴细胞已经迁移远离背神经管。此外，我们检测到相当大的NF 2启动子活性在各种NF 2影响的组织，如听神经节，三叉神经节，脊神经节，视交叉，室管膜细胞含有脉络膜，视网膜色素上皮。在胚胎发育过程中的NF 2启动子表达模式表明，在神经嵴细胞迁移的NF 2基因的特定调节，并进一步支持梅林在细胞粘附，运动和增殖在发展过程中的作用。
Mutations in the Neurofibromatosis 2 (NF2) gene are associated with predisposition to vestibular schwannomas, spinal schwannomas, meningiomas, and ependymomas. Presently, how NF2 is expressed during embryonic development and in the tissues affected by neurofibromatosis type 2 (NF2) has not been well defined. To examine NF2 expression in vivo, we generated transgenic mice carrying a 2.4-kb NF2 promoter driving p-galactosidase (beta-gal) with a nuclear localization signal. Whole-mount embryo staining revealed that the NF2 promoter directed beta-gal expression as early as embryonic day E5.5. Strong expression was detected at E6.5 in the embryonic ectoderm containing many mitotic cells. beta-gal staining was also found in parts of embryonic endoderm and mesoderm. The beta-gal staining pattern in the embryonic tissues was corroborated by in situ hybridization analysis of endogenous Nf2 RNA expression. Importantly, we observed strong NF2 promoter activity in the developing brain and in sites containing migrating cells including the neural tube closure, branchial arches, dorsal aorta, and paraaortic splanchnopleura. Furthermore, we noted a transient change of NF2 promoter activity during neural crest cell migration. While little beta-gal activity was detected in premigratory neural crest cells at the dorsal ridge region of the neural fold, significant activity was seen in the neural crest cells already migrating away from the dorsal neural tube. In addition, we detected considerable NF2 promoter activity in various NF2-affected tissues such as acoustic ganglion, trigeminal ganglion, spinal ganglia, optic chiasma, the ependymal cell-containing tela choroidea, and the pigmented epithelium of the retina. The NF2 promoter expression pattern during embryogenesis suggests a specific regulation of the NF2 gene during neural crest cell migration and further supports the role of merlin in cell adhesion, motility, and proliferation during development.