Laub F, Aldabe R, Friedrich V, Ohnishi S, Yoshida T, Ramirez F
Brookdale Center, Department of Biochemistry and Molecular Biology, Mount Sinai School of Medicine--New York University, One Gustave L. Levy Place, New York, New York 10029, USA.
Dev Biol. 2001 May 15;233(2):305-18. doi: 10.1006/dbio.2001.0243.
To identify potential functions for the Krüppel-like transcription factor KLF7, we have determined the spatiotemporal pattern of gene expression during embryogenesis and in the adult organism. We show that the profile of Klf7 expression predominantly involves the central and peripheral nervous systems and is broadly identified by three separate phases. The first phase occurs early in embryogenesis with increasingly strong expression in the spinal cord, notably in motor neurons of the ventral horn, in dorsal root ganglia, and in sympathetic ganglia. The second robust phase of Klf7 expression is confined to the early postnatal cerebral cortex and is downregulated thereafter. The third phase is characterized by high and sustained expression in the adult cerebellum and dorsal root ganglia. Functionally, these three phases coincide with establishment of neuronal phenotype in embryonic spinal cord, with synaptogenesis and development of mature synaptic circuitry in the postnatal cerebral cortex, and with survival and/or maintenance of function of adult sensory neurons and cerebellar granule cells. Consistent with Klf7 expression in newly formed neuroblasts, overexpression of the gene in cultured fibroblasts and neuroblastoma cells repressed cyclin D1, activated p21, and led to G1 growth arrest. Based on these data, we argue for multiple potential functions for KLF7 in the developing and adult nervous system; they include participating in differentiation and maturation of several neuronal subtypes and in phenotypic maintenance of mature cerebellar granule cells and dorsal root ganglia.
为了确定Krüppel样转录因子KLF7的潜在功能,我们已经确定了其在胚胎发育过程中和成年生物体中的基因表达时空模式。我们发现,Klf7的表达谱主要涉及中枢和外周神经系统,并大致可分为三个不同阶段。第一阶段发生在胚胎发育早期,在脊髓中表达逐渐增强,特别是在腹角运动神经元、背根神经节和交感神经节中。Klf7表达的第二个活跃阶段局限于出生后早期的大脑皮层,随后表达下调。第三阶段的特征是在成年小脑和背根神经节中持续高表达。在功能上,这三个阶段分别与胚胎脊髓中神经元表型的建立、出生后大脑皮层中突触形成和成熟突触回路的发育,以及成年感觉神经元和小脑颗粒细胞的存活和/或功能维持相一致。与Klf7在新形成的神经母细胞中的表达一致,该基因在培养的成纤维细胞和神经母细胞瘤细胞中的过表达抑制了细胞周期蛋白D1,激活了p21,并导致G1期生长停滞。基于这些数据,我们认为KLF7在发育中的和成年的神经系统中具有多种潜在功能;这些功能包括参与几种神经元亚型的分化和成熟,以及成熟小脑颗粒细胞和背根神经节的表型维持。