Song Mi-Ryoung, Shirasaki Ryuichi, Cai Chen-Leng, Ruiz Esmeralda C, Evans Sylvia M, Lee Soo-Kyung, Pfaff Samuel L
Gene Expression Laboratory, The Salk Institute, La Jolla, CA 92037, USA.
Development. 2006 Dec;133(24):4945-55. doi: 10.1242/dev.02694.
Members of the T-box transcription factor family (Tbx) are associated with several human syndromes during embryogenesis. Nevertheless, their functions within the developing CNS remain poorly characterized. Tbx20 is expressed by migrating branchiomotor/visceromotor (BM/VM) neurons within the hindbrain during neuronal circuit formation. We examined Tbx20 function in BM/VM cells using conditional Tbx20-null mutant mice to delete the gene in neurons. Hindbrain rhombomere patterning and the initial generation of post-mitotic BM/VM neurons were normal in Tbx20 mutants. However, Tbx20 was required for the tangential (caudal) migration of facial neurons, the lateral migration of trigeminal cells and the trans-median movement of vestibuloacoustic neurons. Facial cell soma migration defects were associated with the coordinate downregulation of multiple components of the planar cell polarity pathway including Fzd7, Wnt11, Prickle1, Vang1 and Vang2. Our study suggests that Tbx20 programs a variety of hindbrain motor neurons for migration, independent of directionality, and in facial neurons is a positive regulator of the non-canonical Wnt signaling pathway.
T-box转录因子家族(Tbx)的成员在胚胎发育过程中与多种人类综合征相关。然而,它们在发育中的中枢神经系统内的功能仍未得到充分表征。在神经元回路形成过程中,后脑内迁移的鳃弓运动/内脏运动(BM/VM)神经元表达Tbx20。我们使用条件性Tbx20基因敲除小鼠在神经元中删除该基因,研究了Tbx20在BM/VM细胞中的功能。在Tbx20突变体中,后脑菱脑节模式和有丝分裂后BM/VM神经元的初始生成是正常的。然而,Tbx20是面部神经元切向(尾侧)迁移、三叉神经细胞侧向迁移和前庭蜗神经神经元跨中线运动所必需的。面部细胞体迁移缺陷与平面细胞极性途径的多个成分(包括Fzd7、Wnt11、Prickle1、Vang1和Vang2)的协同下调有关。我们的研究表明,Tbx20为多种后脑运动神经元的迁移编程,与方向性无关,并且在面部神经元中是非经典Wnt信号通路的正调节因子。