Developmental Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany.
Dev Biol. 2010 Mar 1;339(1):14-25. doi: 10.1016/j.ydbio.2009.12.003. Epub 2009 Dec 11.
During development, different cell types must undergo distinct morphogenetic programs so that tissues develop the right dimensions in the appropriate place. In early eye morphogenesis, retinal progenitor cells (RPCs) move first towards the midline, before turning around to migrate out into the evaginating optic vesicles. Neighbouring forebrain cells, however, converge rapidly and then remain at the midline. These differential behaviours are regulated by the transcription factor Rx3. Here, we identify a downstream target of Rx3, the Ig-domain protein Nlcam, and characterise its role in regulating cell migration during the initial phase of optic vesicle morphogenesis. Through sophisticated live imaging and comprehensive cell tracking experiments in zebrafish, we show that ectopic expression of Nlcam in RPCs, as is observed in Rx3 mutants, causes enhanced convergence of these cells. Expression levels of Nlcam therefore regulate the migratory properties of RPCs. Our results provide evidence that the two phases of optic vesicle morphogenesis: slowed convergence and outward-directed migration, are under different genetic control. We propose that Nlcam forms part of the guidance machinery directing rapid midline migration of forebrain precursors, where it is normally expressed, and that its ectopic expression upon loss of Rx3 imparts these migratory characteristics upon RPCs.
在发育过程中，不同的细胞类型必须经历不同的形态发生程序，以便组织在适当的位置发育出正确的维度。在早期的眼睛形态发生过程中，视网膜祖细胞 (RPCs) 首先向中线移动，然后再转向迁移到外生的视神经囊中。然而，相邻的前脑细胞迅速汇聚，然后停留在中线。这些不同的行为受转录因子 Rx3 的调节。在这里，我们确定了 Rx3 的下游靶标 Ig 结构域蛋白 Nlcam，并描述了它在调节视神经囊形态发生初始阶段细胞迁移中的作用。通过在斑马鱼中进行复杂的实时成像和全面的细胞跟踪实验，我们表明，如在 Rx3 突变体中观察到的那样，在 RPC 中异位表达 Nlcam 会导致这些细胞的汇聚增强。因此，Nlcam 的表达水平调节 RPCs 的迁移特性。我们的研究结果提供了证据，表明视神经囊形态发生的两个阶段：缓慢的汇聚和向外定向迁移，受不同的遗传控制。我们提出，Nlcam 是指导前脑前体细胞快速中线迁移的导向机制的一部分，在正常情况下表达，而在 Rx3 缺失时异位表达会赋予 RPCs 这些迁移特性。
