Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Shriners Hospital for Children, Boston, MA 02114, USA.
Development. 2020 Dec 23;147(24):dev194498. doi: 10.1242/dev.194498.
and are important for palate development across vertebrates. In zebrafish, we found that regulates the expression of We detailed overlapping and expression in mouse orofacial epithelium. In zebrafish, and share expression in periderm, frontonasal ectoderm and oral epithelium. Genetic disruption of and in zebrafish resulted in cleft of the anterior neurocranium. The mutant also developed cleft of the mouth opening. Lineage tracing of cranial neural crest cells revealed that the cleft resulted not from migration defect, but from impaired chondrogenesis. Analysis of aberrant cells within the cleft revealed expression of , and , and these cells were adjacent to and cells. Breeding of mouse ; ; compound mutants suggested genetic interaction, as the triple homozygote and the ; double homozygote were not observed. Further, heterozygosity reduced cleft severity. These studies highlight the complementary analysis of and in mouse and zebrafish, and identify a unique aberrant cell population in zebrafish expressing , and Future work characterizing this cell population will yield additional insight into cleft pathogenesis.
和 对于脊椎动物的腭发育很重要。在斑马鱼中，我们发现 调节 的表达。我们详细描述了在小鼠口面外胚层中 与 的重叠表达。在斑马鱼中， 和 在表皮、额鼻外胚层和口腔上皮中表达。在斑马鱼中， 和 的基因缺失导致前神经颅裂。 突变体也出现口裂。颅神经嵴细胞的谱系追踪显示，裂的形成不是由于迁移缺陷，而是由于软骨生成受损。对裂隙内异常细胞的分析显示 、 和 的表达，这些细胞与 和 细胞相邻。小鼠 ; ; 复合突变体的繁殖表明存在遗传相互作用，因为未观察到三纯合子和 ; 双纯合子。此外，杂合性降低了 的严重程度。这些研究突出了在小鼠和斑马鱼中对 和 进行互补分析，并确定了在斑马鱼中存在一个表达 、 和 的独特异常细胞群体。进一步的研究特征化这个细胞群体将为腭裂发病机制提供更多的见解。
