Schuff Maximilian, Rössner Antje, Wacker Stephan A, Donow Cornelia, Gessert Susanne, Knöchel Walter
Abteilung Biochemie, Universität Ulm, Ulm, Germany.
Dev Dyn. 2007 Jan;236(1):226-39. doi: 10.1002/dvdy.21007.
A functional knockdown of FoxN3, a member of subclass N of fork head/winged helix transcription factors in Xenopus laevis, leads to an abnormal formation of the jaw cartilage, absence or malformation of distinct cranial nerves, and reduced size of the eye. While the eye phenotype is due to an increased rate of apoptosis, the cellular basis of the jaw phenotype is more complex. The upper and lower jaw cartilages are derivatives of a subset of cranial neural crest cells, which migrate into the first pharyngeal arch. Histological analysis of FoxN3-depleted embryos reveals severe deformation and false positioning of infrarostral, Meckel's, and palatoquadrate cartilages, structural elements derived from the first pharyngeal arch, and of the ceratohyale, which derives from the second pharyngeal arch. The derivatives of the third and fourth pharyngeal arches are less affected. FoxN3 is not required for early neural crest migration. Defects in jaw formation rather arise by failure of differentiation than by positional effects of crest migration. By GST-pulldown analysis, we have identified two different members of histone deacetylase complexes (HDAC), xSin3 and xRPD3, as putative interaction partners of FoxN3, suggesting that FoxN3 regulates craniofacial and eye development by recruiting HDAC.
在非洲爪蟾中，叉头/翼状螺旋转录因子N亚类的成员FoxN3功能缺失会导致颌软骨异常形成、特定颅神经缺失或畸形以及眼睛变小。虽然眼睛表型是由于细胞凋亡率增加所致，但颌表型的细胞基础更为复杂。上下颌软骨是颅神经嵴细胞亚群的衍生物，这些细胞迁移至第一咽弓。对FoxN3缺失胚胎的组织学分析显示，源自第一咽弓的鼻下、梅克尔氏和方骨软骨以及源自第二咽弓的角舌骨严重变形和位置错误。第三和第四咽弓的衍生物受影响较小。早期神经嵴迁移不需要FoxN3。颌形成缺陷不是由嵴迁移的位置效应引起的，而是由分化失败导致的。通过谷胱甘肽-S-转移酶下拉分析，我们鉴定出组蛋白去乙酰化酶复合物（HDAC）的两个不同成员xSin3和xRPD3作为FoxN3的假定相互作用伙伴，这表明FoxN3通过招募HDAC来调节颅面和眼睛发育。
