摘要:

AbstractRecent experiments have begun to decipher the molecular dialog that mediates differentiation at sites of synaptic between neurons and their targets. It had been hypothesized that the protein agrin is released by axon terminals at embryonic neuromuscular junctions and binds to a receptor on the myofiber surface to trigger postsynaptic differentiation. Now a genetic ‘Knockout’ experiment has confirmed the essential role of agrin in signaling between developing nerve and muscle(1). A second ‘knockout’ has shown that the muscle‐specific receptor tyrosine kinase MuSK is a critical element in the agrin‐induced signaling cascade(2). Additional results suggest that MuSK may comprise a portion of the agrin

ISSN:0265-9247    

DOI:10.1002/bies.950181002

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

年代:1996

数据来源: WILEY

摘要:

AbstractThe development of organs during animal development requires the allocation of appropriate numbers of cells to each part of the structure. Yet in Drosophila the patterns of cell proliferation can be quite different from one individual to the next, and in fact can be altered experimentally without altering final morphology. The developing pattern seems to control proliferation, rather than the other way around. Even though the pattern of proliferation is variable, there is some order to it. A recent paper(1)shows that small clusters of cells in developing cell populations are in mitotic synchrony, but that the synchrony is transient. What is the significance of this mitotic synchrony?

ISSN:0265-9247    

DOI:10.1002/bies.950181003

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

年代:1996

数据来源: WILEY

摘要:

AbstractAP‐2 is a recent significant addition to the list of transcription factors that have been demonstrated by targeted gene disruption to be essential for normal development. Two recent reports ofAP‐2null mutant mice(1,2)indicate that AP‐2 holds a key position in the network of genes and proteins controlling developmental pattern and morphogenesis, and that it is particularly important for development of the cranial region and for midline fu

ISSN:0265-9247    

DOI:10.1002/bies.950181004

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

年代:1996

数据来源: WILEY

摘要:

AbstractSpontaneous mutations that perturb myelination occur in a range of species including man, and together with engineered mutations have been used to study disease, normal myelination and axon/glial inter‐relationships. Only a minority of the currently defined mutations have an apparently simple pathogenesis due to lack of a functional protein. Mutations in the myelin basic protein gene lead to a lack of protein, resulting in changes in the structure of myelin, which can be rescued by transgenic complementation. The pathogenesis of autosomal dominant and X‐linked mutations affecting either oligodendrocytes or Schwann cells is more complex. Point mutations may act in a dominant negative manner and gene dosage is clearly linked to phenotypic change. Mutations in regulatory genes, such as those encoding transcription factors, can also disturb myelination by selected cell types. Other less‐well studied and unexpected consequences of myelin mutations, such as seizures in mutations affecting genes expressed in Schwann cells and axonal changes associated with dysmyelination, are also considered. With the major developments in gene mapping and cloning it is now relevant to study mutations in a variety of species with the real prospect of defining their molecular basis. Examples are given of unusual, but potentially useful, uncharacterised mutations in dog and b

ISSN:0265-9247    

DOI:10.1002/bies.950181005

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

年代:1996

数据来源: WILEY

摘要:

AbstractGenetic analysis ofDrosophilhas provided evidence in support of two proposed evolutionary genetic mechanisms of aging: mutation accumulation and antagonistic pleiotropy. Both mechanisms result from the lack of natural selection acting on old organisms. Analyses of large numbers of flies have revealed that mortality rates do not continue to rise with age as previously thought, but plateau at advanced ages. This phenomenon has implications both for models and for definitions of aging, and may be explained by the evolutionary theories. The physiological processes and genes most relevant to aging are being identified usingDrosophilalines selected in the laboratory for postponed senescence. Oxidative stress and insufficient metabolic reserves/capacity may be particularly important factors in limiting the fruitfly lifespan. Genes which exhibit aging‐related changes in expression are now being identified. Transgenic flies are being used to analyze the mechanisms of such aging‐related gene expression, and to test the effects of specific genes on aging and aging‐related deterior

ISSN:0265-9247    

DOI:10.1002/bies.950181006

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

年代:1996

数据来源: WILEY

摘要:

AbstractAgeing is a complex phenomenon which remains a major challenge to modern biology. Although the evolutionary biology of ageing is well understood, the mechanisms that limit lifespan are unknown. The isolation and analysis of single‐gene mutations which extend lifespan (Age mutations) is likely to reveal processes which influence ageing.Caenorhabditis elegansis the only metazoan in which Age mutations have been identified. The Age mutations not only prolong life, but also confer a complex array of other phenotypes. Some of these phenotypes provide clues to the evolutionary origins of these genes while others allude to mechanisms of lifespan‐extension. Many of the Age genes interact and share a second common phenotype, that of stress resistance. Rather than invertebrate ageing being determined by a ‘clock mechanism’, a picture is emerging of ageing as a non‐adaptive process determined, in part, by resistance to intrinsic stress mediated by stress‐res

ISSN:0265-9247    

DOI:10.1002/bies.950181007

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

年代:1996

数据来源: WILEY

摘要:

AbstractIn the mammalian brain dopamine systems play a central role in the control of movement, hormone release, emotional balance and reward. Alteration of dopaminergic neurotransmission is involved in Parkinson's disease and other movement disorders, as well as in some psychotic syndromes. This review summarises recent findings, which shed some light on signals and cellular interactions involved in the specification and maturation of the dopaminergic function during neurogenesis. In particular we will focus on three major issues: (1) the differentiation of dopaminergic neurones triggered by direct contact with the midbrain floor plate cells through the action of sonic hedgehog; (2) the neurotrophic factors acting on dopaminergic neurones; and (3) the role of target striatal cells on the survival and the axonal growth of developing or grafted dopaminergic neurones.

ISSN:0265-9247    

DOI:10.1002/bies.950181008

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

年代:1996

数据来源: WILEY

摘要:

AbstractX‐linked agammaglobulinemia is a heritable immunodeficiency disease caused by a differentiation abnormality, resulting in the virtual absence of B Iymphocytes and plasma cells. The affected gene encodes a cytoplasmic protein tyrosine kinase, Bruton's agammaglobulinemia tyrosine kinase, designated Btk. Btk and the other family members, Tec, Itk and Bmx, contain five regions, four of which are common structural and functional modules that are found in other signaling proteins. Mutations affect all domains of the gene, but amino acid substitutions seem to be confined to certain regions. More than 150 unique mutations have been identified and are collected in a mutation database, BTKbase. Here we discuss the three‐dimensional structural implications of such mutations and their putative functional role. Of special interest are mutations affecting the pleckstrin homology domain, as Btk is the only disease‐associated protein so far reported to carry mutations in this particular m

ISSN:0265-9247    

DOI:10.1002/bies.950181009

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

年代:1996

数据来源: WILEY

摘要:

AbstractWhilst the role of Maturation or M‐phase Promoting Factor (MPF) as a universal M‐phase regulator is well documented, much less attention has been paid to its role in nuclear transplantation experiments and especially to its influence upon remodelling of transplanted nuclei. There is currently wide acceptance that successful nuclear transplantation using differentiated nuclei is possible only in a cytoplasmic environment that is capable of inducing rapid nuclear de‐differentiation to a pronuclear‐like form. In this review our purpose is firstly, to outline the conditions under which such remodelling can be induced, and secondly, to extend the debate to include a consideration of whether complete nuclear remodelling is an absolute necessity for clonal deve

ISSN:0265-9247    

DOI:10.1002/bies.950181010

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

年代:1996

数据来源: WILEY

摘要:

AbstractThe mechanisms responsible for the fine tuning of development, where the wildtype phenotype is reproduced with high fidelity, are not well understood. The difficulty in approaching this problem is the identification of mutant phenotypes indicative of a defect in these fine‐tuning control mechanisms. Evolutionary biologists have used asymmetry as a measure of developmental homeostasis. The rationale for this was that, since the same genome controls the development of the left and right sides of a bilaterally symmetrical organism, departures from symmetry can be used to measure genetic or environmental perturbations. This paper examines the relationship between asymmtry and resistance to organophosphorous insecticides in the Australian sheep blowfly,Lucilia cuprina.A resistance gene,Rop‐1, which encodes a carboxylesterase enzyme, also confers a significant increase in asymmetry. Continued exposure of resistant populations to insecticide has selected a dominant suppressor of the asymmetry phenotype. Genetic evidence indicates that the modifier is theL. cuprina Notchhomolo

ISSN:0265-9247    

DOI:10.1002/bies.950181011

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

年代:1996

数据来源: WILEY