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F Laub

Publications and source records attributed to F Laub.

10 recordsLinked to original sources

Developmental expression of mouse Krüppel-like transcription factor KLF7 suggests a potential role in neurogenesis.

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.

Amino Acid Sequence↗

Embryonic expression of type XIX collagen is transient and confined to muscle cells.

Type XIX collagen is a poorly characterized extracellular matrix component thought to be involved in the formation of specialized basement membrane zones. Here we examined the developmental expression of the mouse gene (Col19a1) by in situ hybridization. Col19a1 expression during embryogenesis commences at approximately E9.5 in the myotome and with a pattern that closely follows the myogenic regulatory factor myf-5. Like myf-5, Col19a1 transcription gradually decreases in differentiating skeletal muscle progenitors and concomitantly to increased myogenin gene expression. Transient expression of Col19a1 in muscular tissues is confined to a few sites of the developing embryo, such as limbs, tongue, and the smooth muscle layers of the stomach and esophagus. Additional non-muscular sites of Col19a1 activity include the skin of the E16.5 embryos and the cerebral cortex and hippocampus of the new born brain. Unlike all other tissues, expression of Col19a1 in the central nervous system gradually increases after birth.

Animals↗

Embryonic expression of Krüppel-like factor 6 in neural and non-neural tissues.

Mammalian Krüppel-like transcription factors include 12 zinc finger proteins (KLF1-12) that are involved in regulation of cell proliferation and differentiation during morphogenesis and development (Trends Biochem. Sci., 24 (1999) 236). Structural considerations have segregated KLF6 and KLF7 into a separate sub-group, whereas in situ hybridizations have revealed predominant expression of the mouse klf7 gene in the developing nervous system. We examined the embryonic pattern of mouse klf6 in order to assess whether close kinship between KLF6 and KLF7 reflects similar expression patterns of the genes. The results of the in situ hybridizations demonstrate that klf6 expression in the developing nervous system is more restricted than klf7. In contrast to klf7, we also identified several non-neural sites of strong klf6 expression; they include the developing hindgut, heart, lung, kidney, and autopod.

Animals↗

Overexpression of a novel zinc-finger protein induces apoptosis in NIH3T3 fibroblasts.

Genes coding for zinc-finger proteins constitute about 1% of the mammalian genome. Here we report the cloning of a novel mouse gene (Zfp319) encoding a nuclear protein with 11 zinc-finger motifs of the C2H2 type. Zfp319 consists of two exons, the second of which contains the entire coding sequence. Preliminary evidence suggests that the primary transcript undergoes alternative splicing with the potential of producing Zfp319 isoforms that contain different numbers of zinc fingers or none. The Zfp319 gene maps to chromosome 8, in a region of conserved synteny with the human counterpart on chromosome 16. Finally, overexpression of the Zfp319 protein in stably transfected fibroblasts results in significant reduction of viable cells due to induction of programmed cell death.

3T3 Cells↗

Developmental expression of the mouse gene coding for the Krüppel-like transcription factor KLF5.

The mammalian Krüppel-like transcription factors are key regulators of multiple morphogenetic programs. Here, we examined the developmental expression of the mouse Klf5 gene and compared it to the established pattern of the Klf4 gene. The results revealed that the two genes are expressed in both overlapping and mutually exclusive patterns. Unlike Klf4, Klf5 mRNA is detected in the E15.5 meninges and in the E.16.5 epithelium of trachea and bronchi. Both genes are co-expressed in the outer layer of the tongue, as well as in the developing epidermis and gut with interesting temporal differences. Klf4 expression in the skin gradually decreases from E15.5 on, whereas Klf5 transcripts continue to accumulate at a fairly high rate in the basal layer of the epidermis. The same sustained activity of Klf5 is already seen in the gastrointestinal tract of the 10.5 day embryo, and is later confined to the base of the intestinal crypts. Maximal Klf4 expression in the gastrointestinal tract is limited to a narrower window of time during the late phase of development.

Animals↗

Cloning the cDNA for a new human zinc finger protein defines a group of closely related Krüppel-like transcription factors.

We have identified a novel zinc finger protein that has been named ubiquitous Krüppel-like factor (UKLF) based on structural considerations and the pattern of gene expression. UKLF was isolated by the polymerase chain reaction approach using degenerate oligonucleotides corresponding to the DNA-binding domain of erythroid Krüppel-like factor (EKLF) and cDNA prepared from human vascular endothelial cells. The carboxyl-terminal portion of UKLF contains three zinc fingers of the Cys2-His2 type and binds in vitro to the CACCC motif of the beta-globin promoter and to the Sp1 recognition sequence. The amino-terminal portion of UKLF consists of a hydrophobic region rich in serines and a negatively charged segment with several glutamic acid residues. The first 47 amino acids of the acidic region are nearly identical to the amino-terminal portion of another Krüppel-like factor, the so-called core promoter-binding protein (CPBP) or Zf9. Like CPBP/Zf9, UKLF can function as a transcription activator in co-transfection assays. However, this activity is lost when the highly conserved amino-terminal segment is deleted. These findings indicate that UKLF and CPBP/Zf9 represent a distinct subgroup of closely related Krüppel-like activators of transcription. Mapping of the UKLF gene to chromosome 2 suggested that UKLF and CPBP/Zf9 translocated to different chromosomes following duplication from an ancestral gene.

Amino Acid Sequence↗

Actin polymerization induced by pulsed electric stimulation of bone cells in vitro.

Electric field pulses, capacitively applied to tissue cultures of embryonic bone cells, were shown to induce changes in the state of cellular actin. Three actin states could be defined by DNAase I inhibition. A rapidly (20-30 s) inhibiting fraction, attributed to monomeric G-actin, amounts to 55% of total actin in nonstimulated cells. An additional fraction of 8% required approx. 20 min to reach full inhibition and was tentatively defined as polymeric 'F'-actin. The remaining 37% could be detected only after treatment of the cells with 0.75 M guanidine hydrochloride, which dissociates actin from all its protein interactions. This fraction, N-actin (network actin) is believed to represent F-actin integrated into some supramolecular structure, where it is not accessible to DNAase I. Upon short electric stimulation the distribution changed to 40% G-actin, 12% F-actin and 48% N-actin. 3-Isobutyl-1-methylxanthine (IBMX; an inhibitor of cAMP phosphodiesterase), depletion of extracellular calcium, and calmodulin inhibitors abolished this field effect.

1-Methyl-3-isobutylxanthine↗

The state of actin in activated human platelets.

The state of platelet actin was determined using a fluorescent method of DNAse I inhibition. Activation of human platelets resulted in mobilization of DNAse-available actin. When platelets were activated with ADP the change in the state of actin was gradual and preceded the secretion. When thrombin was used as an activator, a sharp and rapid decrease in the DNAse-available actin was observed which paralleled the secretion. Inhibition of ADP-induced aggregation (and secretion) by EDTA resulted in a decrease in the rate of change on actin. Inhibition of the thrombin-induced aggregation (but not secretion) by EDTA did not affect the change in the state of actin.

Actins↗