Regulatory signals and signal molecules in early neurogenesis of Drosophila melanogaster

Summary The ectodermal germ layer of Drosophila melanogaster gives rise to two major cell lineages, the neural and the epidermal. Progenitor cells for each of these lineages arise from groups of cells, whose elements must decide between taking on either fate. Commitment of the progenitor cells to one of the developmental fates implies two factors. One is intrinsic to the ectodermal cells and determines a propensity to take on neural fate; this factor is probably represented by the products of the so-called proneural genes, which are differentially distributed throughout the ectoderm. The other factor in the cells' decision to adopt one of the two alternative fates is intercellular communication, which is mediated by the products of the so-called neurogenic genes. Two types of interactions, one inhibiting and the other stimulating neural development, have been inferred. We discuss here the assumed role of various neurogenic genes, in particular Notch and Delta, in these processes.Offprint requests to: J.A. Campos-Ortega     

果蝇衰老的调控机制

衰老是一个复杂的生物学过程,涉及到有害物质的积累导致整体生命功能的下降,生物的生理状况逐渐恶化,最终导致疾病和死亡。黑腹果蝇Drosophila melanogaster作为最重要的遗传学工具之一,近年来常被用于衰老的研究,以阐明衰老的发生与发展机制。本文结合本实验室的研究进展,综述了果蝇寿命调控的生理生化机制,如保幼激素、胰岛素/类胰岛素生长因子、TOR信号网络、腺苷酸活化蛋白激酶信号通路、热量限制和饮食限制、氧化应激、小分子RNA以及鞘脂类代谢都会对果蝇的寿命产生影响。除此之外,基因调控网络研究还能够发现潜在的与长寿相关的基因组区域,将有可能发现更多寿命相关基因。以果蝇为模式生物的研究,对于其他昆虫衰老、存活等种群生物学问题的研究以及天敌、益虫保育和害虫控制,具有十分重要的指导意义。     

Mutations of early neurogenesis inDrosophila

Summary Embryonic lethal mutations at the Notch locus are known to produce a conspicuous central nervous system hypertrophy accompanied by a hypotrophy of the epidermal sheath. We have studied several zygotic mutants belonging to four different autosomal complementation groups which produce the same phenotype. The embryonic development of the new mutants, as well as that of Notch, consists of an initial enlargement of the neurogenic region at the expenses of epidermal cell precursors. The possibility is discussed that these five loci are involved in the determination of neural and epidermal cell precursors.     

Drosophila melanogaster P Transposable Elements: Mechanisms of Transposition and Regulation

The molecular mechanisms that control P element transposition and determine its tissue specificity remain incompletely understood, although much information has been compiled about this element in the last decade. This review summarizes the currently available information about P element transposition, P-M hybrid dysgenesis and P cytotype features, P element-encoded repressors, and regulation of transposition.     

The molecular genetics of early neurogenesis in Drosophila melanogaster

The extent of neurogenesis in Drosophila is under the control of the so-called neurogenic genes, named for their mutant phenotype of causing neural hyperplasia. Their wild-type products appear to be responsible for a signal chain that decides the fate of ectodermal cells in the embryo. Various kinds of data, from cell transplantation experiments as well as from genetic and molecular analyses, suggest that the proteins encoded by the genes Notch and Delta may act at the membrane of the signal-transmitting cells to provide a ligand to a still unknown receptor molecule; in contrast, the locus of Enhancer of split codes for several functions related to the transduction and further processing of the signal.     

Evidence for genomic regulation of the telomeric activity in Drosophila melanogaster

The structural integrity of TART elements has been used as reporter of instability at chromosomal ends in numerous Drosophila stocks and over time in an unstable stock. The results show that telomeric activity is a regulated process that may differ between the stocks as well as over time within a stock. This revised version was published online in July 2006 with corrections to the Cover Date.     

A functional analysis of the genes Enhancer of split and HLH-m5 during early neurogenesis in Drosophila melanogaster

To assess the functional domains of the proteins encoded by E(spl) and HLH-m5, two genes of the Enhancer of split complex [E(SPL)-C] of Drosophila melanogaster, a number of variants have been made by in vitro mutagenesis, transformed into the germ line of the wild-type, and genetically combined with a chromosomal deletion lacking four of the genes of the E(SPL)-C. All constructs used attenuated the neurogenic phenotype associated with this deletion. However, constructs encoding proteins with truncated carboxy-termini exibited in all cases a higher activity than constructs encoding the full length version of the protein. Neutralization of the basic domain severely reduced, but did not completely abolish the rescuing activity of E(spl), while proteins in which a proline residue within the basic domain had been changed to either threonine or asparagine were slightly less efficient in their rescuing activity than the corresponding wild-type versions. We discuss the possible significance of these results for the function of the protein domains.     

Genetic mechanisms of early neurogenesis inDrosophila melanogaster

The neurogenic ectoderm ofDrosophila melanogaster consists of the ventral neuroectoderm and the procephalic neuroectoderm. It is hypothesized that epidermal and central neural progenitor cells separate from each other in three steps: conference on the neuroectodermal cells the capability of producing neural or epidermal progenies, separation of the two classes of progenitor cells, and specification of particular types of neuroblasts and epidermoblasts. Separation of neuroblasts and epidermoblasts in controlled by proneural and neurogenic genes.Delta andNotch serve as mediators of direct protein-protein interactions. E(spl)-C inhibits neurogenesis, creating epidermal cells. The achaete-scute complex (AS-C) controls the commitment of nonoverlapping populations of neuroblasts and leads the development of neuroectodermal cells as neuroblasts.     

Mating increases starvation resistance and decreases oxidative stress resistance in Drosophila melanogaster females

Mating stimulates complex physiological changes in females of Drosophila melanogaster. Long-term effects of mating are manifested in increased fecundity and shortened lifespan. It is not clear how mating affects stress resistance in fly females. We addressed this question here and found that mated and highly fecund wild-type D. melanogaster females have significantly higher resistance to starvation throughout their lifetime than age-matched virgin females. Mean survival time under starvation was age dependent with maximum survival time observed in 15-day-old mated females. Mating-induced increase in starvation resistance was associated with significantly higher fat reserves stored as triacylglycerols. While mated females had higher resistance to starvation, their resistance to oxidative stress was significantly lower than in age-matched virgins. Our study revealed that mating leads to an opposing relationship between resistance to starvation and resistance to oxidative stress in Drosophila females. Thus, shortened lifespan of mated females is associated with their high-fat content and greater susceptibility to oxidative stress.     

P element regulation and X-chromosome subtelomeric heterochromatin in Drosophila melanogaster

In Drosophila melanogaster, crossing males carrying autonomous P elements with females devoid of P copies results in hybrid dysgenesis in the germline of progeny. The reciprocal cross produces non-dysgenic progeny due to a maternally inherited state non-permissive for P transposition. The capacity of a P copy to repress transposition depends on both its structure and its chromosomal location. Naturally occuring regulatory P elements inserted at the telomere of the X chromosome have been genetically isolated in a genomic context devoid of other P elements. One or two copies of autonomous P elements at this site (1A) are sufficient to elicit a strong P repression in the germline. These elements are flanked by Telomeric Associated Sequences, previously identified and described by Karpen and Spradling (1992) as having heterochromatic properties. The regulatory properties of P elements at 1A are strongly impaired by mutations affecting Su(var)205, which encodes Heterochromatin Protein 1, a non-histone heterochromatin protein. The regulatory properties of classical P strains are not sensitive to Su(var)205. Models based on chromatin structure or on nuclear localisation of the telomeres are discussed in order to explain both the strong regulatory properties of P elements at the X chromosome telomere and their sensitivity to Su(var)205. This revised version was published online in August 2006 with corrections to the Cover Date.     

Two-step regulation of ecdysone-inducible late puffs in salivary glands of Drosophila melanogaster

Our previous study showed that some ecdysone-inducible late puffs could also be induced by a mild detergent (digitonin) in Drosophila salivary glands. However, they could only be induced at the stage immediately prior to when developmentally programmed puffing occurred, suggesting that these late puff loci were under two-step regulation. Using an in vitro culture of salivary glands, we have examined whether ecdysone or the protein products of early puff genes participate in either of the two steps of late puff regulation. This study has revealed that (i) the acquisition of digitonin-responsiveness (the first step) could be induced in vitro by incubating salivary glands with ecdysone; (ii) the first step could also be induced by protein synthesis inhibition even in the absence of ecdysone; (iii) the second step required both ecdysone and protein synthesis unless treated with digitonin; and (iv) the first step, rather than the second step, determines the timing of normal puff formation in the loci. These results suggest that, during normal development, ecdysone controls both steps by activating two types of early genes; the first type, whose function can be mimicked by cycloheximide, renders the loci responsive to digitonin and the second type, whose function can be mimicked by digitonin, activates the loci to form puffs.     

Maintenance of transposable element copy number in natural populations of Drosophila melanogaster and D. simulans

To investigate the main forces controlling the containment of transposable elements (TE) in natural populations, we analyzed the copia, mdg1, and 412 elements in various populations of Drosophila melanogaster and D. simulans. A lower proportion of insertion sites on the X chromosome in comparison with the autosomes suggests that selection against the detrimental effects of TE insertions is the major force containing TE copies in populations of Drosophila. This selection effect hypothesis is strengthened by the absence of the negative correlation between recombination rate and TE copy number along the chromosomes, which was expected under the alternative ectopic exchange model (selection against the deleterious rearrangements promoted by recombination between TE insertions). A cline in 412 copy number in relation to latitude was observed among the natural populations of D. simulans, with very high numbers existing in some local populations (around 60 copies in a sample from Canberra, Australia). An apparent absence of selection effects in this Canberra sample and a value of transposition rate equal to 1–2 × 10^-3 whatever the population and its copy number agree with the idea of recent but temporarily drastic TE movements in local populations. The high values of transposition rate in D. simulans clearly disfavor the hypothesis that the low amount of transposable elements in this species could result from a low transposition rate. This revised version was published online in August 2006 with corrections to the Cover Date.     

Simulation of gene pyramiding in Drosophila melanogaster

Gene pyramiding has been successfully practiced in plant breeding for developing new breeds or lines in which favorable genes from several different lines were integrated.But it has not been used in animal breeding,and some theoretical investigation and simulation analysis with respect to its strategies,feasibility and efficiency are needed before it can be implemented in animals.In this study,we used four different pure fines of Drosophila melanogaster,each of which is homozygous at a specific mutant gene with a visible effect on phenotype,to simulate the gene pyramiding process and analyze the duration and population size required in different pyramiding strategies.We finally got the ideal individuals,which are homozygous at the four target genes simultaneously.This study demonstrates that gene pyramiding is feasible in animal breeding and the interaction between genes may affect the final results.     

Simulation of gene pyramiding in Drosophila melanogaster

Gene pyramiding has been successfully practiced in plant breeding for developing new breeds or lines in which favorable genes from several different lines were integrated.But it has not been used in animal breeding,and some theoretical investigation and simulation analysis with respect to its strategies,feasibility and efficiency are needed before it can be implemented in animals.In this study,we used four different pure lines of Drosophila melanogaster,each of which is homozygous at a specific mutant gene ...     

Molecular mechanisms of early neurogenesis in vertebrates

Recent studies revealed a great variety of genes which control the early development of the central nervous system in vertebrates, including neural induction and differentiation of primary neurons. Most of these genes were first identified inDrosophila melanogaster, then their structural and functional homologs were found in vertebrates. Modern data on the molecular-genetic mechanisms of vertebrate neurogenesis are reviewed. The neurogenetic mechanisms are compared for vertebrates and invertebrates. Widely discussed hypotheses are considered along with the commonly accepted mechanisms.     

Naturally occurring quantitative variants of acid phosphatase-1 in Drosophila melanogaster

We have examined 111 wild Drosophila melanogaster lines for cis-acting quantitative variants of the Acph-1 gene, which codes for acid phosphatase-1 (ACPH). Three variants with obvious, reproducible phenotypes were isolated. All variants acted equally on all tissues and developmental stages examined. No recombinants were detected between one quantitative variant and the site determining the electrophoretic mobility of Acph-1 among 3885 flies examined. Several enzymatic properties of the variant enzymes were tested, including the K_mvalues for two substrates, inhibition by three different inhibitors, and thermal stability; the variant enzymes behaved identically to the wild-type enzyme in all cases. Immunological titration experiments showed that the variant enzymes had the same enzyme activity per molecule of ACPH as the wild-type enzyme. These results suggest that the quantitative variants we have identified are altered in the regulatory portion of Acph-1 so as to produce altered numbers of normal ACPH molecules.This work was supported by NIH Grant 21548. MAJ was supported by NIH Predoctoral Training Grant GM07413.     

果蝇蛋白质组学研究进展

蛋白质组学旨在阐明基因组所表达的真正执行生命活动的全部蛋白质的表达规律和生物功能。随着人类基因组学计划的逐渐成熟,分子水平的实验技术不断发展,蛋白质组学的研究被提高到了前所未有的高度。果蝇是生命科学领域最为常用的一种模式生物,长期的系统研究也使果蝇的基因组成为至今注释最好的基因组之一,为功能基因组研究奠定了基础。但由于技术的限制,迄今有关果蝇蛋白质组学研究的报道尚不多见。近年来果蝇蛋白质组学的研究主要包括表达谱、修饰谱、比较蛋白质组学和疾病模型蛋白质组等四个方向,为进一步开展人类疾病临床蛋白质组学研究奠定了基础。     

Functions of the segment polarity genes midline and H15 in Drosophila melanogaster neurogenesis

The Drosophila melanogaster ventral nerve cord derives from neural progenitor cells called neuroblasts. Individual neuroblasts have unique gene expression profiles and give rise to distinct clones of neurons and glia. The specification of neuroblast identity provides a cell intrinsic mechanism which ultimately results in the generation of progeny which are different from each other. Segment polarity genes have a dual function in early neurogenesis: within distinct regions of the neuroectoderm, they are required both for neuroblast formation and for the specification of neuroblast identity. Previous studies of segment polarity gene function largely focused on neuroblasts that arise within the posterior part of the segment. Here we show that the segment polarity gene midline is required for neuroblast formation in the anterior-most part of the segment. Moreover, midline contributes to the specification of anterior neuroblast identity by negatively regulating the expression of Wingless and positively regulating the expression of Mirror. In the posterior-most part of the segment, midline and its paralog, H15, have partially redundant functions in the regulation of the NB marker Eagle. Hence, the segment polarity genes midline and H15 play an important role in the development of the ventral nerve cord in the anterior- and posterior-most part of the segment.     

Constitutive heterochromatin and transposable elements in Drosophila melanogaster

Several families of transposable elements (TEs), most of them belonging to the retrotransposon catagory, are particularly enriched in Drosophila melanogaster constitutive heterochromatin. The enrichment of TE-homologous sequences into heterochromatin is not a peculiar feature of the Drosophila genome, but appears to be widespread among higher eukaryotes. The constitutive heterochromatin of D. melanogaster contains several genetically active domains; this raises the possibility that TE-homologous sequences inserted into functional heterochromatin compartments may be expressed. In this review, I present available data on the genetic and molecular organization of D. melanogaster constitutive heterochromatin and its relationship with transposable elements. The implications of these findings on the possible impact of heterochromatic TEs on the function and evolution of the host genome are also discussed. This revised version was published online in August 2006 with corrections to the Cover Date.