摘要:

AbstractGenomic imprinting is an epigenetic mechanism resulting in the preferential expression of the maternal or paternal alleles of a specific subset of genes in the mammalian genome. A key but relatively unexplored question is how imprints are established in the germline. New observations(1)on two classical imprinting disorders, the Prader‐Willi (PWS) and Angleman (AS) syndromes, offer the first genetic insight into this process. Molecular analysis of imprinting mutations that interfere with the appropriate establishment of the maternal and paternal epigenotypes has led to the identification of imprinted transcripts that could be involved in switching imprints in the germline

ISSN:0265-9247    

DOI:10.1002/bies.950190502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractTranscription in organisms as diverse as yeast and mammals is subject to chromosomal position effects that result in heritable and variegated patterns of gene expression. Two recent studies have employed a reversible protein‐DNA crosslinking method to identify the structural components of heterochromatin in budding yeast(1,2). The results show that a complex containing the proteins Rap1, Sir2p, Sir3p and Sir4p is physically associated with nucleosomes at telomere proximal regions, but that the repressive chromatin structure extended by Sir3p overexpression has a different compositio

ISSN:0265-9247    

DOI:10.1002/bies.950190503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractAt fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+concentration. The precise sequence of events that occur between sperm‐egg contact and the increases in intracellular Ca2+remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that specifically comigrates with Ca2+oscillation‐inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+oscillations may have wider physiological significance since sperm oscillin can induce Ca2+oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+oscillati

ISSN:0265-9247    

DOI:10.1002/bies.950190504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractHoxcomplex genes are key developmental regulators highly conserved throughout evolution. The encoded proteins share a 60‐amino‐acid DNA‐binding motif, the homeodomain, and function as transcription factors to control axial patterning. An important question concerns the nature and function of genes acting downstream of Hox proteins. This review focuses onDrosophila, as little is known about this question in other organisms. The noticeable progress gained in the field during the past few years has significantly improved our current understanding of howHoxgenes control diversified morphogenesis. Here we summarise the strategies deployed to identifyHoxtarget genes and discuss how their function contributes to pattern formation and morphogenesis. The regulation of target genes is also considered with special emphasis on the mechanisms underlying the specificity of action of Hox proteins in the whole a

ISSN:0265-9247    

DOI:10.1002/bies.950190505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractHirschsprung disease and the multiple endocrine neoplasia type 2 syndromes are hereditary disorders related to the abnormal migration, proliferation or survival of neural crest cells and their derivatives. Hirschsprung disease is a frequent disorder of the enteric nervous system, resulting in intestinal obstruction. The multiple endocrine neoplasia type 2 syndromes predispose to cancers of neural crest derivatives. Both diseases are associated with heterozygous mutations in theRETproto‐oncogene.RETencodes a transmembrane receptor tyrosine kinase expressed in neural crest lineages and whose ligand, glial‐cell‐line‐derived neurotrophic factor, has been very recently identified.In vitroexpression studies demonstrate that while Hirschsprung disease mutations result in loss of function of the mutant RET tyrosine kinase, multiple endocrine neoplasia type 2 mutations lead to its constitutive activation. Thus, the two ‘faces’ of RET, gain of function and loss of function, each lead to a different syndrome, respectively: multiple endocrine neoplasia type 2, a cancer syndrome, or Hirschsprung disease, a developme

ISSN:0265-9247    

DOI:10.1002/bies.950190506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractThe life cycle ofDictyostelium discoideumoffers a unique opportunity to study signal transduction in eukaryotic cells at both the unicellular and multicellular levels of organization. Adding to the already extensive knowledge of the unicellular stages, classical and molecular genetics have begun to unravel transduction of signals controlling morphogenesis and behaviour (phototaxis and thermotaxis) in the multicellular ‘slug’ stage of the life cycle. Distributed over all seven genetic linkage groups are probably about 20, but possibly as many as 55, genes of importance for slug behaviour. The encoded proteins appear from pharmacological studies and mutant phenotypes to govern transduction pathways involving the intracellular second messengers cyclic AMP, cyclic GMP, IP3and Ca2+. Pathways from the photo‐ and thermoreceptors converge first with each other and thence, at the level of the second messengers, with those from extracellular tip activation (cyclic AMP) and inhibition (Slug Turning Factor and/or ammonia and/or adenosine) signals that control slug movement and morphoge

ISSN:0265-9247    

DOI:10.1002/bies.950190507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractSex is determined by non‐Mendelian genetic elements overriding the sex factors carried by the heterochromosomes in some species of terrestrial isopods. A bacteriumWolbachiaand a non‐bacterial feminizing factor (f) can both force chromosomal males ofArmadillidium vulgareto become phenotypic functional females. The f factor is believed to be a genetic element derived from theWolbachiagenome that becomes inserted into the host nuclear genome. The feminizing factors can be considered to be selfish genetic elements because they bias their host's sex ratio to increase their own transmission. New sex‐determining genes are selected (genes resisting the feminizing effects, or the transmission of feminizing elements) as a consequence of the conflict between these elements and the rest of the host's genome. These events drive the sex‐determining mechanisms to evolve, and may explain the polymorphism of sex factors and the poor differentiation of the heterochromosomes in

ISSN:0265-9247    

DOI:10.1002/bies.950190508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractPhosphotyrosine phosphatases (PTPases) are the enzymes which remove phosphate groups from protein tyrosine residues. An enormous number of phosphatases have been cloned and sequenced during the past decade, many of which are expressed in haematopoietic cells. This review focuses on the biochemistry and cell biology of three phosphatases, the transmembrane CD45 and the cytosolic SH2‐domain‐containing PTPases SHP‐1 and SHP‐2, to illustrate the diverse ways in which PTPases regulate receptor signal transduction. The involvement of these and other PTPases has been demonstrated in haematopoietic cell development, apoptosis, activation and non‐responsiveness. A common theme in the actions of many haematopoietic cell PTPases is the way in which they modulate the thresholds for receptor signalling, thereby regulating critical events in the positive and negative selection of lymphocytes. There is growing interest in haematopoietic PTPases and their associated regulatory proteins as targets for pharmaceutical intervention and in the involvement of these enzymes in huma

ISSN:0265-9247    

DOI:10.1002/bies.950190509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractThe sudden appearance in the fossil record of the major animal phyla apparently records a phase of unparalleled, rapid evolution at the base of the Cambrian period, 545 Myr ago. This has become known as the Cambrian evolutionary ‘explosion’, and has fuelled speculation about unique evolutionary processes operating at that time. The acceptance of the palaeontological evidence as a true reflection of the evolutionary narrative has been criticised in two ways: from a reappraisal of the phylogenetic relationships of the early fossils, and from predicitions of molecular divergence times, based on six appropriate metazoan genes. Phylogenetic analysis of the arthropods implies an earlier, Precambrian history for most clades, and hence an extensive period of cladogenesis unrecorded by fossils. A similar argument can be applied to molluscs, lophophorates and deuterostomes. Molecular evidence implies divergence between clades to at least 1000 Myr ago. The apparent paradox between the sudden appearance of recognisable metazoans and their extended evolutionary history might be explained by a sudden Cambrian increase in body size, which was accompanied by skeletisation. A new paradigm suggests that the ‘explosion’ in the record may have been decoupled from the evolutionary inn

ISSN:0265-9247    

DOI:10.1002/bies.950190510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY

摘要:

AbstractDevelopment of a vaccine for schistosomiasis, a parasitic disease currently affecting over 200 million people worldwide, has been targeted as a priority by the World Health Organisation. Research demonstrating the ability of humans to acquire natural immunity to schistosome infection, together with the successful use of attenuated vaccines in animals both under laboratory and field conditions, suggest that development of a human vaccine is feasible. Attenuated vaccines for schistosomiasis are considered neither safe nor practicable for human use, however, and therefore other approaches must be considered. This review examines progress currently being undertaken in a number of different areas towards achieving the goal of a safe and effective human vaccine for schistosomiasis.

ISSN:0265-9247    

DOI:10.1002/bies.950190511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1997

数据来源: WILEY