Department of Biological Sciences, University of Alberta, CW405, Biological Sciences Bldg, Edmonton T6G 2E9, Canada.
Neural Dev. 2010 Sep 1;5:22. doi: 10.1186/1749-8104-5-22.
During visual system development, multiple signalling pathways cooperate to specify axial polarity within the retina and optic tectum. This information is required for the topographic mapping of retinal ganglion cell axons on the tectum. Meis1 is a TALE-class homeodomain transcription factor known to specify anterior-posterior identity in the hindbrain, but its role in visual system patterning has not been investigated.
meis1 is expressed in both the presumptive retina and tectum. An analysis of retinal patterning reveals that Meis1 is required to correctly specify both dorsal-ventral and nasal-temporal identity in the zebrafish retina. Meis1-knockdown results in a loss of smad1 expression and an upregulation in follistatin expression, thereby causing lower levels of Bmp signalling and a partial ventralization of the retina. Additionally, Meis1-deficient embryos exhibit ectopic Fgf signalling in the developing retina and a corresponding loss of temporal identity. Meis1 also positively regulates ephrin gene expression in the tectum. Consistent with these patterning phenotypes, a knockdown of Meis1 ultimately results in retinotectal mapping defects.
In this work we describe a novel role for Meis1 in regulating Bmp signalling and in specifying temporal identity in the retina. By patterning both the retina and tectum, Meis1 plays an important role in establishing the retinotectal map and organizing the visual system.
在视觉系统发育过程中,多种信号通路协同作用,在视网膜和视顶盖内指定轴向极性。这些信息是视网膜神经节细胞轴突在顶盖表面进行拓扑映射所必需的。Meis1 是一种 TALE 类同源结构域转录因子,已知在后脑中指定前后身份,但它在视觉系统模式形成中的作用尚未得到研究。
meis1 在预期的视网膜和视盖中均有表达。对视网膜模式形成的分析表明,Meis1 是正确指定斑马鱼视网膜中背腹和鼻颞身份所必需的。Meis1 敲低导致 smad1 表达的丧失和 follistatin 表达的上调,从而导致 Bmp 信号水平降低和视网膜部分腹侧化。此外,Meis1 缺陷胚胎在发育中的视网膜中表现出异位 Fgf 信号,并且颞侧身份丧失。Meis1 还在视顶盖中正向调节 Ephrin 基因的表达。与这些模式形成表型一致,Meis1 的敲低最终导致视网膜顶盖映射缺陷。
在这项工作中,我们描述了 Meis1 在调节 Bmp 信号和指定视网膜中颞侧身份方面的新作用。通过对视网膜和视顶盖进行模式形成,Meis1 在建立视网膜顶盖映射和组织视觉系统方面发挥着重要作用。