- Email: [email protected]
EMF, an Arabidopsis gene required for vegetative shoot development
~ONITOR
A 'digest' of s o m e recent papers of interest in the primary journals.
Molecularcharacterization of the mouse agouti locus S.J. BULTMAN, E.J. MICHAUD AND R.P. WOYCHIK
Cell 71, 1195--1204 The agouti locus of the mouse has held a special fascination ever since the days of the mouse fancy. Agouti acts within the hair follicle to make each hair black with a band of yellow near the top: the true wild-type coloration of the mouse coat. Certain alleles at agouti also affect embryonic development, for example the yellow (AY) allele has dominant pleiotropic effects including obesity and diabetes, but is a recessive embryonic lethal. Bultman et al. have now cloned
Putative fragile sites in the horse ka~otype M. RONNE
Hereditas 117, 127-136 Fragile sites on human chromosomes have been in the news recently, with the identification of an unstable trinucleotide repeat associated with a rare fragile site on the X chromosome that is linked with a form of mental retardation. But FRAXA is only one of 107 known
EMF,an Arabtdopsts gene required for vegetative shoot development :'..R. SLING, A. BELACHEW, B. SHUNONG AND R. BERTIIAND-GARCIA
Science 258, 1645-1647 What controls the transition from a vegetative meristem to an inflorescence meristem to initiate flowering? Sung et al. have found a locus in Arabidopsis that seems to be important for this transition. Mutants at this
Prevention of programmedcell death in Caenorhabditiselegans by human bcl.2 D.L. VAUX, I.L. WEISSMAN AND S.K. KIM
Science 258, 1955-1957 Death - cell death, that is - is part of life. Of the 1090 somatic cells formed during the development of the nematode worm C. elegans, 131 are destined to die soon after their birth, while both the nen,ous and immune systems of mammals rely for t h e i r p r o p e r development on cell death on a massive scale. Recently, genes implicated in such 'programmed cell deaths' have been
agouti. They had previously obtained a radiation-induced inversion that had breakpoints within agouti and the limb deformity (ld) loci; this allowed them to 'jump' into agouti using an id probe. Zoo blots identified a conserved region within the cloned DNA that was shown to give rise to a 0.8 kb transcript in the skin of newborn mice. No other tissues contained transcripts except testis, where a range of transcripts were found that are of unknown significance. Probes specific for the cloned locus detected structural alterations in five mutant alleles of agouti, strengthening the evidence that the cloned locus is indeed agouti. The product of the locus is predicted to be
a 15 kDa protein that may contain an amino-terminal signal peptide (perhaps indicating that it is secreted from the follicle cells, as the genetics suggests) but has no obvious sequence similarity to other known proteins. Interestingly, Av homozygotes were found to express high levels of an abnormal transcript of agoutf in all of their tissues; this may be responsible for the dominant pleiotropic effects of the mutation. Molecular analysis of the ,,9' transcript showed that it contains a novel sequence replacing exon I of the wild-type transcript. Bultman et al. speculate that it may be disruption of this other sequence that is responsible for the recessive embryonic lethality.
fragile sites in humans - sites at which chromosomes are prone to breakage after various chemical treatments or thymidine starvation. The other 106 have not so far been associated with any phenotype. Fragile sites in other mammals have received less attention, but have been reported, for example, in pigs, rabbits, dogs and a variety of rodents including the laboratory mouse. Ronne reports the first demonstration of fragile sites in the horse karyotype. In
blood samples from 15 horses, a total of 12 different fragile sites were observed when cultures were synchronized in S phase by treatment with fluorouracil, then released by addition of 5-bromodeoxyuridine (BUdR). Some of these sites could be correlated with folate and/or BUdR-sensitive fragile sites in syntenic regions of other mammalian chromosomes, including human, suggesting that some fragile sites are widely conserved among mammals, a~
locus, which they call EMF, were selected on the basis that homozygotes germinated to produce not a normal rosette-like plant, but several cauline leaves (aerial leaves produced after floral induction) and multiple flower buds that gave rise to abnormal flowers. That is, the mutants produced an inflorescence meristem without first producing a vegetative shoot. The shoot apical meristem of the mutants was enlarged and abhor-
mal in shape when compared with wild-type. Sung et ai. suggest that, if the recessive emf mutation is a lossof-function mutation, the function of the wild-type EMF gene may be to suppress the development of the reproductive state of the shoot apical meristem. In response to signals such as long-day conditions, the amount of EMF product may diminish, triggering the transition from vegetative to inflorescence meristem.
identified in both worms and mammals, so it was tempting to see whether there are any functional similarities that extend across this huge evolution~"y" divide. Vaux et al. have approached this question by expressing the haman BCL-2 gene in transgenic worms, under the control of a heat shock promoter and linked to an identifiable marker gene. BCL-2 was originally discovered because w h e n improperly activated by a chromosomal translocation it causes human follicular lymphoma. It has since been implicated in preventing cell deaths both of myeloid and neuronal cells. Transgenic worms expressing
BCL-2 showed less than half the number of visible cell deaths during embryonic development. This reduction was not due just to more rapid engulfment of the cell corpses. BCL-2 behaves most like the C. elegans gene ced-9, which protects cells against cell death and is antagonized in cells that are destined to die by the action of ced-3 and ced-4. The fact that BCL-2works in worms suggests that there are likely to be mammalian functional homologues of ced-3 and/or ced-4. From worms to humans, it aopears that in programmed cell death the Pale Horseman uses the same henchmen, a~
"FIGMARCH1993 VOL.9 NO. 3
m
A 'digest' of s o m e recent papers of interest in the primary journals.
Molecularcharacterization of the mouse agouti locus S.J. BULTMAN, E.J. MICHAUD AND R.P. WOYCHIK
Cell 71, 1195--1204 The agouti locus of the mouse has held a special fascination ever since the days of the mouse fancy. Agouti acts within the hair follicle to make each hair black with a band of yellow near the top: the true wild-type coloration of the mouse coat. Certain alleles at agouti also affect embryonic development, for example the yellow (AY) allele has dominant pleiotropic effects including obesity and diabetes, but is a recessive embryonic lethal. Bultman et al. have now cloned
Putative fragile sites in the horse ka~otype M. RONNE
Hereditas 117, 127-136 Fragile sites on human chromosomes have been in the news recently, with the identification of an unstable trinucleotide repeat associated with a rare fragile site on the X chromosome that is linked with a form of mental retardation. But FRAXA is only one of 107 known
EMF,an Arabtdopsts gene required for vegetative shoot development :'..R. SLING, A. BELACHEW, B. SHUNONG AND R. BERTIIAND-GARCIA
Science 258, 1645-1647 What controls the transition from a vegetative meristem to an inflorescence meristem to initiate flowering? Sung et al. have found a locus in Arabidopsis that seems to be important for this transition. Mutants at this
Prevention of programmedcell death in Caenorhabditiselegans by human bcl.2 D.L. VAUX, I.L. WEISSMAN AND S.K. KIM
Science 258, 1955-1957 Death - cell death, that is - is part of life. Of the 1090 somatic cells formed during the development of the nematode worm C. elegans, 131 are destined to die soon after their birth, while both the nen,ous and immune systems of mammals rely for t h e i r p r o p e r development on cell death on a massive scale. Recently, genes implicated in such 'programmed cell deaths' have been
agouti. They had previously obtained a radiation-induced inversion that had breakpoints within agouti and the limb deformity (ld) loci; this allowed them to 'jump' into agouti using an id probe. Zoo blots identified a conserved region within the cloned DNA that was shown to give rise to a 0.8 kb transcript in the skin of newborn mice. No other tissues contained transcripts except testis, where a range of transcripts were found that are of unknown significance. Probes specific for the cloned locus detected structural alterations in five mutant alleles of agouti, strengthening the evidence that the cloned locus is indeed agouti. The product of the locus is predicted to be
a 15 kDa protein that may contain an amino-terminal signal peptide (perhaps indicating that it is secreted from the follicle cells, as the genetics suggests) but has no obvious sequence similarity to other known proteins. Interestingly, Av homozygotes were found to express high levels of an abnormal transcript of agoutf in all of their tissues; this may be responsible for the dominant pleiotropic effects of the mutation. Molecular analysis of the ,,9' transcript showed that it contains a novel sequence replacing exon I of the wild-type transcript. Bultman et al. speculate that it may be disruption of this other sequence that is responsible for the recessive embryonic lethality.
fragile sites in humans - sites at which chromosomes are prone to breakage after various chemical treatments or thymidine starvation. The other 106 have not so far been associated with any phenotype. Fragile sites in other mammals have received less attention, but have been reported, for example, in pigs, rabbits, dogs and a variety of rodents including the laboratory mouse. Ronne reports the first demonstration of fragile sites in the horse karyotype. In
blood samples from 15 horses, a total of 12 different fragile sites were observed when cultures were synchronized in S phase by treatment with fluorouracil, then released by addition of 5-bromodeoxyuridine (BUdR). Some of these sites could be correlated with folate and/or BUdR-sensitive fragile sites in syntenic regions of other mammalian chromosomes, including human, suggesting that some fragile sites are widely conserved among mammals, a~
locus, which they call EMF, were selected on the basis that homozygotes germinated to produce not a normal rosette-like plant, but several cauline leaves (aerial leaves produced after floral induction) and multiple flower buds that gave rise to abnormal flowers. That is, the mutants produced an inflorescence meristem without first producing a vegetative shoot. The shoot apical meristem of the mutants was enlarged and abhor-
mal in shape when compared with wild-type. Sung et ai. suggest that, if the recessive emf mutation is a lossof-function mutation, the function of the wild-type EMF gene may be to suppress the development of the reproductive state of the shoot apical meristem. In response to signals such as long-day conditions, the amount of EMF product may diminish, triggering the transition from vegetative to inflorescence meristem.
identified in both worms and mammals, so it was tempting to see whether there are any functional similarities that extend across this huge evolution~"y" divide. Vaux et al. have approached this question by expressing the haman BCL-2 gene in transgenic worms, under the control of a heat shock promoter and linked to an identifiable marker gene. BCL-2 was originally discovered because w h e n improperly activated by a chromosomal translocation it causes human follicular lymphoma. It has since been implicated in preventing cell deaths both of myeloid and neuronal cells. Transgenic worms expressing
BCL-2 showed less than half the number of visible cell deaths during embryonic development. This reduction was not due just to more rapid engulfment of the cell corpses. BCL-2 behaves most like the C. elegans gene ced-9, which protects cells against cell death and is antagonized in cells that are destined to die by the action of ced-3 and ced-4. The fact that BCL-2works in worms suggests that there are likely to be mammalian functional homologues of ced-3 and/or ced-4. From worms to humans, it aopears that in programmed cell death the Pale Horseman uses the same henchmen, a~
"FIGMARCH1993 VOL.9 NO. 3
m