Fleming R J, Scottgale T N, Diederich R J, Artavanis-Tsakonas S
Howard Hughes Medical Institute, Department of Cell Biology, Yale University, New Haven, Connecticut 06511.
Genes Dev. 1990 Dec;4(12A):2188-201. doi: 10.1101/gad.4.12a.2188.
Mutations in the third chromosome gene Serrate are shown to display genetic interactions with specific alleles of the neurogenic locus Notch, which encodes a transmembrane protein with epidermal growth factor (EGF) homology. Embryonic lethal Serrate mutations exhibit epidermal and neuronal defects, which are reminiscent of those produced by mutations in the Drosophila EGF receptor homolog gene. We present the molecular cloning of Serrate and show that it encodes two coordinately expressed transcripts from a genomic interval greater than 30 kb in length. The deduced protein product of 1404 amino acids contains a single transmembrane domain and 14 EGF-like repeats. Thus, Serrate represents another member of the group of EGF-containing loci in Drosophila. Whole-mount in situ hybridization analysis reveals complex temporal and spatial patterns of RNA expression consistent with the epidermal and neuronal defects observed in mutant embryos. Finally, we discuss the implications of Serrate function within the context of other cell-surface molecules known to be involved in the differentiation of ectodermally derived tissues.
第三染色体基因锯齿（Serrate）中的突变显示出与神经源基因座Notch的特定等位基因存在遗传相互作用，Notch编码一种具有表皮生长因子（EGF）同源性的跨膜蛋白。胚胎致死性锯齿突变表现出表皮和神经元缺陷，这让人联想到果蝇EGF受体同源基因中的突变所产生的缺陷。我们展示了锯齿基因的分子克隆，并表明它从一个长度大于30kb的基因组区间编码两个协同表达的转录本。推导的1404个氨基酸的蛋白质产物包含一个单一的跨膜结构域和14个EGF样重复序列。因此，锯齿代表了果蝇中含EGF基因座组的另一个成员。全胚胎原位杂交分析揭示了RNA表达复杂的时空模式，这与在突变胚胎中观察到的表皮和神经元缺陷一致。最后，我们在已知参与外胚层来源组织分化的其他细胞表面分子的背景下讨论了锯齿功能的意义。
