Challa Anil K, McWhorter Michelle L, Wang Chunping, Seeger Mark A, Beattie Christine E
Center for Molecular Neurobiology, Department of Molecular Genetics, The Ohio State University, Columbus, OH 43210, USA.
Mech Dev. 2005 Oct;122(10):1073-86. doi: 10.1016/j.mod.2005.06.006.
Roundabout (Robo) receptors and their secreted ligand Slits have been shown to function in a number of developmental events both inside and outside of the nervous system. We previously cloned zebrafish robo orthologs to gain a better understanding of Robo function in vertebrates. Further characterization of one of these orthologs, robo3, has unveiled the presence of two distinct isoforms, robo3 variant 1 (robo3var1) and robo3 variant 2 (robo3var2). These two isoforms differ only in their 5'-ends with robo3var1, but not robo3var2, containing a canonical signal sequence. Despite this difference, both forms accumulate on the cell surface. Both isoforms are contributed maternally and exhibit unique and dynamic gene expression patterns during development. Functional analysis of robo3 isoforms using an antisense gene knockdown strategy suggests that Robo3var1 functions in motor axon pathfinding, whereas Robo3var2 appears to function in dorsoventral cell fate specification. This study reveals a novel function for Robo receptors in specifying ventral cell fates during vertebrate development.
已知Roundabout（Robo）受体及其分泌配体Slits在神经系统内外的许多发育过程中发挥作用。我们之前克隆了斑马鱼Robo直系同源基因，以便更好地了解Robo在脊椎动物中的功能。对其中一个直系同源基因robo3的进一步研究发现了两种不同的异构体，即robo3变体1（robo3var1）和robo3变体2（robo3var2）。这两种异构体仅在其5'端有所不同，robo3var1含有一个典型的信号序列，而robo3var2没有。尽管存在这种差异，但两种形式都在细胞表面积累。两种异构体均由母体提供，并在发育过程中表现出独特且动态的基因表达模式。使用反义基因敲低策略对robo3异构体进行功能分析表明，Robo3var1在运动轴突导向中起作用，而Robo3var2似乎在背腹细胞命运特化中起作用。这项研究揭示了Robo受体在脊椎动物发育过程中确定腹侧细胞命运方面的新功能。
