Dougherty Max, Kamel George, Shubinets Valeriy, Hickey Graham, Grimaldi Michael, Liao Eric C
Division of Plastic and Reconstructive Surgery and Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Craniofac Surg. 2012 Sep;23(5):1333-7. doi: 10.1097/SCS.0b013e318260f20b.
Cranial neural crest cells follow stereotypic patterns of migration to form craniofacial structures. The zebrafish is a powerful vertebrate genetic model where transgenics with reporter proteins under the transcriptional regulation of lineage-specific promoters can be generated. Numerous studies demonstrate that the zebrafish ethmoid plate is embryologically analogous to the mammalian palate. A fate map correlating embryonic cranial neural crest to defined jaw structures would provide a useful context for the morphogenetic analysis of craniofacial development. To that end, the sox10:kaede transgenic was generated, where sox10 provides lineage restriction to the neural crest. Specific regions of neural crest were labeled at the 10-somite stage by photoconversion of the kaede reporter protein. Lineage analysis was carried out during pharyngeal development in wild-type animals, after miR140 injection, and after estradiol treatment. At the 10-somite stage, cranial neural crest cells anterior of the eye contributed to the median ethmoid plate, whereas cells medial to the eye formed the lateral ethmoid plate and trabeculae and a posterior population formed the mandible. miR-140 overexpression and estradiol inhibition of Hedgehog signaling resulted in cleft development, with failed migration of the anterior cell population to form the median ethmoid plate. The sox10:kaede transgenic line provides a useful tool for neural crest lineage analysis. These studies illustrate the advantages of the zebrafish model for application in morphogenetic studies of vertebrate craniofacial development.
颅神经嵴细胞遵循刻板的迁移模式以形成颅面结构。斑马鱼是一种强大的脊椎动物遗传模型，在此模型中可以生成在谱系特异性启动子转录调控下带有报告蛋白的转基因动物。大量研究表明，斑马鱼筛板在胚胎学上类似于哺乳动物的腭。将胚胎颅神经嵴与特定颌骨结构相关联的命运图谱将为颅面发育的形态发生分析提供有用的背景信息。为此，构建了sox10:kaede转基因动物，其中sox10对神经嵴进行谱系限制。在10体节期通过对kaede报告蛋白进行光转化来标记神经嵴的特定区域。在野生型动物、注射miR140后以及雌二醇处理后的咽发育过程中进行谱系分析。在10体节期，眼睛前方的颅神经嵴细胞形成正中筛板，而眼睛内侧的细胞形成外侧筛板和小梁，后方的一群细胞形成下颌骨。miR - 140过表达和雌二醇对Hedgehog信号通路的抑制导致腭裂发育，前方细胞群迁移失败，无法形成正中筛板。sox10:kaede转基因系为神经嵴谱系分析提供了一个有用的工具。这些研究说明了斑马鱼模型在脊椎动物颅面发育形态发生研究中的应用优势。
