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Cystic fibrosis mouse with intestinal obstruction
~IoNITOR Spatial pattern of cdc2 expression in relation to meristem activity and cell proliferation during plant development
Recently, cDNAs corresponding to the Arabidopsis homologue of the yeast c d c 2 / C D C 2 8 gene, which has a crucial role in controlling progression of the cell cycle, were cloned. Martinez et aL have used
in situ hybridization to study expression of the gene during plant development. They found high levels of transcripts in tissues that contained actively proliferating cells, for example root and shoot meristems, and leaf and flower primordia. Tissues that were relatively mitotically inactive, such as the quiescent centre of the root, or the apical cell layers of the flower primordia, contained lower concentrations of transcripts. A detailed study of CDC2 expression in the
developing flower revealed strong expression in the basal regions of developing floral organs and in the developing vascular system - a reciprocal pattern of expression to that of the floral homeotic genes AGAMOUS and APETALA 3. Martinez et al. suggest that there may be mutual regulation of genes controlling cell proliferation and differentiation during plant development, and that plants may offer a useful system for studying developmental regulation of cell cycle genes such as cdc2.
The involvement of the Notch locus in Drosophila 00genesis
An animal model for cystic fibrosis made by gene targeting
T. KU, L.A. CARON, R.G. FEHON AND S. ARTAVANIS-TSAKONAS
Science 257, 1083-1088
mutagenesis of the mouse Cfir gene. Interestingly, the severity of CF symptoms in the homozygous mutants varied: the mice produced by the North Carolina group (Snouwaert et al. and Clarke et al.) showed intestinal blockage, severe pancreatic insufficiency and early death, as did those produced by the Cambridge group (Colledge et al.), while the Edinburgh group's mice (Dorin et al.) were more mildly affected, showing mild pathology of the gut, lungs and vas deferens. The different targeting vectors used by the three groups may provide an explanation for these differences, as the insertional vector used by the Edinburgh group could allow some restoration of gene function by splicing out of the insert. However, genetic background may also play some part. The mouse model should allow the effects of other genetic variables to be investigated, and also provides a valuable system for trying out routes to gene therapy for CF.
M.C. MARTINEZ ETAL.
Proc. Natl A c a d . Sci. USA 89,
7360-7364
D e v e l o p m e n t 115, 913-922
The Notch protein is best known for its role in cell--cell interactions involved in epidermal/neural cell fate decisions. However, it now appears to be remarkably pleiotropic, with involvement in early neurogenesis, late bristle formation, eye development and oogenesis. Xu et aL have examined the distribution of the Notch protein in oogenesis and the effects of the Notch temperaturesensitive mutation m tsl (which is shown to be a missense mutation in the extracellular domain that is homologous to epidermal growth factor), both on Notch protein expression and on oocyte development. They also show that Notch is expressed during spermatogenesis, consistent with the effect of N tsl on male fertility. In oogenesis, Notch is expressed on both the somatically derived follicle cells and in the germ-line nurse cells. Notch protein is strikingly polarized to the apical surfaces of the follicle cells, perhaps reflecting a function in signalling between the follicular envelope and the oocyte. In N tsl mutants at the nonpermissive temperature, this polarity is much less obvious, and oocyte development is abnormal, with the formation of large irregular nurse cell--oocyte complexes. Several processes appear disrupted and one of the earliest defects is possibly the failure to form the specialized stalk follicle cells that separate successive nurse cell-oocyte complexes. Thus Notch may again be involved in the regulation of cell fate decisions. The pleiotropy of Notch suggests that it is used as a common component of cell--cell interactions that in different tissues may be linked to more specific induction mechanisms.
J.N. SNOUWAERT ETA&
Defective epit,helial chloride transport in a gene-targeted mouse model of cystic fibrosis L.L. CLARKE ETAL.
Science 257, 1125-1128
Cystic fibrosis in the mouse by targeted inserti0nal mutagenesis J.R. DORIN ETAL.
N a t u r e 359, 211-215
Cystic fibrosis mouse with intestinal obstruction W.H. COLLEDGE E T A L
L a n c e t 340, 680
With the remarkable synchrony that seems characteristic of so many advances in human genetics, three groups have virtually simultaneously succeeded in making a mouse model for cystic fibrosis (CF) by targeted
Involvement of the $1314global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae Y.W. JIANG AND D.I. STILLMAN
Mol. Cell. Biol. 12, 4503-4514
In this issue of T/G, Winston and Carlson discuss two groups of yeast genes, the SNF/SWI genes and the SPT/SIN genes, that appear to have global regulatory effects on transcription via effects on chromatin structure. Jiang and Stillman now implicate the SIN4 gene in such phenomena. A sin4 mutant was first isolated as a suppressor of s w i 5 mutations, allowing expression from the H O promoter in the absence of SWI5. Jiang and Stillman now show that a sin4A null mutation also suppresses s w i 2 and s w i 4 mutations, suppresses an insertion mutation caused by a 8 element (a long terminal repeat of the Ty transposon), TIG NOVEMBER1992 VOL.8 NO. 11
and suppresses the effects of s w i 2 and s w i I mutations on transcription of the SUC2 gene. These results suggest that SIN4 acts as a transcriptional repressor, like the SPT/SIN proteins that are postulated to maintain an inactive state of chromatin (for details, see review by Winston and Carlson). But surprisingly, a SIN4-LEXA fusion protein activated transcription from promoters containing LEXA binding sites, indicating instead a role for SIN4 more akin to that of the SNF/SWI activators. Jiang and Stillman suggest that this apparent contradiction can be reconciled by the notion that a generalized affect on chromatin structure, mediated by SIN4, could in different situations have either positive or negative regulatory effects. They demonstrate an effect of SIN4 on chromatin structure by showing that the sin4A null mutation alters the superhelical density of a circular plasmid.
Recently, cDNAs corresponding to the Arabidopsis homologue of the yeast c d c 2 / C D C 2 8 gene, which has a crucial role in controlling progression of the cell cycle, were cloned. Martinez et aL have used
in situ hybridization to study expression of the gene during plant development. They found high levels of transcripts in tissues that contained actively proliferating cells, for example root and shoot meristems, and leaf and flower primordia. Tissues that were relatively mitotically inactive, such as the quiescent centre of the root, or the apical cell layers of the flower primordia, contained lower concentrations of transcripts. A detailed study of CDC2 expression in the
developing flower revealed strong expression in the basal regions of developing floral organs and in the developing vascular system - a reciprocal pattern of expression to that of the floral homeotic genes AGAMOUS and APETALA 3. Martinez et al. suggest that there may be mutual regulation of genes controlling cell proliferation and differentiation during plant development, and that plants may offer a useful system for studying developmental regulation of cell cycle genes such as cdc2.
The involvement of the Notch locus in Drosophila 00genesis
An animal model for cystic fibrosis made by gene targeting
T. KU, L.A. CARON, R.G. FEHON AND S. ARTAVANIS-TSAKONAS
Science 257, 1083-1088
mutagenesis of the mouse Cfir gene. Interestingly, the severity of CF symptoms in the homozygous mutants varied: the mice produced by the North Carolina group (Snouwaert et al. and Clarke et al.) showed intestinal blockage, severe pancreatic insufficiency and early death, as did those produced by the Cambridge group (Colledge et al.), while the Edinburgh group's mice (Dorin et al.) were more mildly affected, showing mild pathology of the gut, lungs and vas deferens. The different targeting vectors used by the three groups may provide an explanation for these differences, as the insertional vector used by the Edinburgh group could allow some restoration of gene function by splicing out of the insert. However, genetic background may also play some part. The mouse model should allow the effects of other genetic variables to be investigated, and also provides a valuable system for trying out routes to gene therapy for CF.
M.C. MARTINEZ ETAL.
Proc. Natl A c a d . Sci. USA 89,
7360-7364
D e v e l o p m e n t 115, 913-922
The Notch protein is best known for its role in cell--cell interactions involved in epidermal/neural cell fate decisions. However, it now appears to be remarkably pleiotropic, with involvement in early neurogenesis, late bristle formation, eye development and oogenesis. Xu et aL have examined the distribution of the Notch protein in oogenesis and the effects of the Notch temperaturesensitive mutation m tsl (which is shown to be a missense mutation in the extracellular domain that is homologous to epidermal growth factor), both on Notch protein expression and on oocyte development. They also show that Notch is expressed during spermatogenesis, consistent with the effect of N tsl on male fertility. In oogenesis, Notch is expressed on both the somatically derived follicle cells and in the germ-line nurse cells. Notch protein is strikingly polarized to the apical surfaces of the follicle cells, perhaps reflecting a function in signalling between the follicular envelope and the oocyte. In N tsl mutants at the nonpermissive temperature, this polarity is much less obvious, and oocyte development is abnormal, with the formation of large irregular nurse cell--oocyte complexes. Several processes appear disrupted and one of the earliest defects is possibly the failure to form the specialized stalk follicle cells that separate successive nurse cell-oocyte complexes. Thus Notch may again be involved in the regulation of cell fate decisions. The pleiotropy of Notch suggests that it is used as a common component of cell--cell interactions that in different tissues may be linked to more specific induction mechanisms.
J.N. SNOUWAERT ETA&
Defective epit,helial chloride transport in a gene-targeted mouse model of cystic fibrosis L.L. CLARKE ETAL.
Science 257, 1125-1128
Cystic fibrosis in the mouse by targeted inserti0nal mutagenesis J.R. DORIN ETAL.
N a t u r e 359, 211-215
Cystic fibrosis mouse with intestinal obstruction W.H. COLLEDGE E T A L
L a n c e t 340, 680
With the remarkable synchrony that seems characteristic of so many advances in human genetics, three groups have virtually simultaneously succeeded in making a mouse model for cystic fibrosis (CF) by targeted
Involvement of the $1314global transcriptional regulator in the chromatin structure of Saccharomyces cerevisiae Y.W. JIANG AND D.I. STILLMAN
Mol. Cell. Biol. 12, 4503-4514
In this issue of T/G, Winston and Carlson discuss two groups of yeast genes, the SNF/SWI genes and the SPT/SIN genes, that appear to have global regulatory effects on transcription via effects on chromatin structure. Jiang and Stillman now implicate the SIN4 gene in such phenomena. A sin4 mutant was first isolated as a suppressor of s w i 5 mutations, allowing expression from the H O promoter in the absence of SWI5. Jiang and Stillman now show that a sin4A null mutation also suppresses s w i 2 and s w i 4 mutations, suppresses an insertion mutation caused by a 8 element (a long terminal repeat of the Ty transposon), TIG NOVEMBER1992 VOL.8 NO. 11
and suppresses the effects of s w i 2 and s w i I mutations on transcription of the SUC2 gene. These results suggest that SIN4 acts as a transcriptional repressor, like the SPT/SIN proteins that are postulated to maintain an inactive state of chromatin (for details, see review by Winston and Carlson). But surprisingly, a SIN4-LEXA fusion protein activated transcription from promoters containing LEXA binding sites, indicating instead a role for SIN4 more akin to that of the SNF/SWI activators. Jiang and Stillman suggest that this apparent contradiction can be reconciled by the notion that a generalized affect on chromatin structure, mediated by SIN4, could in different situations have either positive or negative regulatory effects. They demonstrate an effect of SIN4 on chromatin structure by showing that the sin4A null mutation alters the superhelical density of a circular plasmid.