Kuang B, Wu S C, Shin Y, Luo L, Kolodziej P
Howard Hughes Medical Institute, Department of Cell Biology, Vanderbilt University Medical Center, Nashville TN 37232-0295, USA.
Development. 2000 Apr;127(7):1517-29. doi: 10.1242/dev.127.7.1517.
split ends (spen) encodes nuclear 600 kDa proteins that contain RNA recognition motifs and a conserved C-terminal sequence. These features define a new protein family, Spen, which includes the vertebrate MINT transcriptional regulator. Zygotic spen mutants affect the growth and guidance of a subset of axons in the Drosophila embryo. Removing maternal and zygotic protein elicits cell-fate and more general axon-guidance defects that are not seen in zygotic mutants. The wrong number of chordotonal neurons and midline cells are generated, and we identify defects in precursor formation and EGF receptor-dependent inductive processes required for cell-fate specification. The number of neuronal precursors is variable in embryos that lack Spen. The levels of Suppressor of Hairless, a key transcriptional effector of Notch required for precursor formation, are reduced, as are the nuclear levels of Yan, a transcriptional repressor that regulates cell fate and proliferation downstream of the EGF receptor. We propose that Spen proteins regulate the expression of key effectors of signaling pathways required to specify neuronal cell fate and morphology.
“分裂端”（split ends，spen）编码核内600 kDa的蛋白质，这些蛋白质包含RNA识别基序和保守的C末端序列。这些特征定义了一个新的蛋白质家族Spen，其中包括脊椎动物的MINT转录调节因子。合子型spen突变体影响果蝇胚胎中一部分轴突的生长和导向。去除母源和合子型蛋白质会引发细胞命运以及更普遍的轴突导向缺陷，而这些缺陷在合子型突变体中并未出现。产生了错误数量的弦音神经元和中线细胞，并且我们确定了前体形成以及细胞命运特化所需的表皮生长因子受体依赖性诱导过程中的缺陷。在缺乏Spen的胚胎中，神经元前体的数量是可变的。对于前体形成所必需的Notch关键转录效应因子“无毛抑制因子”（Suppressor of Hairless）的水平降低，同样，作为在表皮生长因子受体下游调节细胞命运和增殖的转录抑制因子，“Yan”的核水平也降低。我们提出，Spen蛋白调节指定神经元细胞命运和形态所需信号通路的关键效应因子的表达。
