摘要:

The National Institutes of Health funding mechanisms, which were so successful in the past, are now much less effective. The problems are caused by the low percentage of applications that can be supported with the limited funds available, and by the inability of the peer‐review system to operate under these extreme conditions. The quality of applications immediately above and immediately below the funding line is not significantly different. Moreover, the situation continues to deteriorate, creating serious additional problems and undermining the morale of scientists and the future of American science. It is extremely difficult for the young investigator to acquire funding, and it is an unpredictable roulette for the established investigator. To solve the present crisis, we propose to modify current policy so as to regulate the minimum percent effort necessary to carry out different classes of projects, and to limit the funds that most investigators could obtain. We also propose to replace the all‐or‐none cutoff line by a sliding scale that will provide funding roughly proportional to the quality of the applications. Efforts should be made to provide deserving investigators, whose proposals are not funded, with short‐term emergency funds to avoid the disintegration of research teams before they can reapply. The implementation and regulation of these changes will be difficult, but the stability and wider distribution of research support are expected to have a profoundly beneficial effect on the quality and originality of American science and on the morale of scientists. Besides the changes in funding policy, the scientific community must continue working with Congress to identify and implement better solutions to the problems, namely to assure growth in the support of basic biomedical research and training, and for targeted research in the most critical areas.— Musacchio, J. M. American science in crisis: the need to revise the NIH funding policy.FASEB J.8: 679‐683; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.7832841

出版商:Wiley    

年代:1994

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/j.1530-6860.1994.tb93361.x

出版商:Wiley    

年代:1994

数据来源: WILEY

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050665

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Neural induction is the process during early embryonic development whereby the mesoderm of the embryo elicits a change of fate in cells of the overlying ectoderm, from epidermal to neural. Since its discovery in 1924 by Spemann and Mangold, who used newt embryos, most research on this developmental event has been conducted with urodelean and anuran amphibians. This is because of the ease with which they can be manipulated and because of the recent availability of cell type‐ and region‐specific molecular markers. With the recent isolation and characterization of suitable markers in the chick embryo, and the equal ease with which it can be manipulated, the way is now open for amniote embryos to join amphibians as an experimental system for neural induction studies. Another advantage of the avian embryo is that it possesses a peripheral extraembryonic region, which although it does not contribute to embryonic tissues at all, is competent to respond to neural‐inducing signals, thereby providing developmentally naive cells for in vivo and in vitro assays. Here, I review recent advances that make the chick embryo a system uniquely suited for the study of neural induction at both the cellular and the molecular level.—Stern, C. D. The avian embryo: a powerful model system for studying neural induction.FASEB J.8: 687‐691; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050666

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Zebrafish embryos represent an attractive system for the study of early vertebrate neurogenesis. The embryos develop outside of the mother and are transparent allowing analysis at the cellular level in the living embryo during all phases of early neurogenesis. The teleostean neural tube is generated by a mechanism different from that of other vertebrates. A massive keel is formed first and the central canal appears by subsequent cavitation. Despite this, however, the organization of the neural plate and the neural keel resembles that of other vertebrates in many aspects. Oriented cell divisions coupled with oriented cell intercalations appear to be involved in the morphogenesis of the neural keel. Embryos mutant in thecyclopsgene show deficiencies in the ventral neural tube. They lack the floor plate and the ventral parts of the diencephalon. Two recently cloned genes,axialandsonic hedgehog, have been implicated in the development of the ventral midline of the neural tube. Expression ofaxialandsonic hedgehogis impaired by thecyclopsmutation in the midline of the neural plate. This, together with the effects of ectopic expression of the two cloned genes, suggests thataxial, sonic hedgehog, andcyclopsare part of the regulatory cascade leading to floor plate formation.— Strähle, U., Blader, P. Early neurogenesis in the zebrafish embryo.FASEB J.8: 692‐698; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050667

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Neural crest cells arise from the neural tube shortly after its closure and migrate extensively through prescribed regions of the embryos, where they differentiate into most of the peripheral nervous system as well as the facial skeleton and pigment cells. Along the embryonic axis, several distinct neural crest populations differ both in their migratory pathways and range of derivatives. Whereas those cells arising from the midbrain migrate as a uniform sheet of cells, neural crest cells emerging from the hindbrain and trunk regions migrate in a segmented manner. For example, trunk neural crest cells move preferentially through the rostral, but not caudal, half of each somite. Interactions with tissues encountered during migration strongly influence this segmental migratory pattern. For example, the mesodermal somites dictate the segmental migration of trunk neural crest cells and the otic placode appears to attract hindbrain neural crest cells. Although little is known about the molecular basis underlying migration, patterns of gene expression in the hindbrain are thought to contribute to the segmental arrangement of neural crest cells. Furthermore, neural crest cells possess integrin receptors that may be important for interacting with extracellular matrix molecules in their surroundings.— Bronner‐Fraser, M. Neural crest cell formation and migration in the developing embryo.FASEB J.8: 699‐706; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050668

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

The neural crest is a migratory population of multipotent embryonic cells that generates the neurons and glia of the peripheral nervous system, as well as a variety of non‐neural mesectodermal and endocrine cell types. The study of neural crest cell and molecular biology provides a system to investigate how such multipotent cells choose their fates, and whether the repertoire of fates becomes progressively restricted with time. The study of mammalian neural crest development has lagged behind studies of avian crest development due to the relative inaccessibility of mammalian embryos. The development of reverse genetic methods in mice, however, has made the analysis of mammalian neural crest development both more attractive and more tractable. Rodent neural crest cells have been isolated and grown in clonogenic cultures, where they behave as multipotent stem cells. This system provides an assay for factors that influence the differentiation of these multipotent cells. Transcription factors provide valuable early markers for neural crest cells as well as molecular handles on the lineage segregation process. One such factor isMash1, a homolog of theDrosophilaproneural genes,achaete‐scute.Mash1 marks autonomic progenitor cells and is essential for their development in vivo, as shown by gene knockout experiments.—Anderson, D. J. Stem cells and transcription factors in the development of the mammalian neural crest.FASEB J.8: 707‐713; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050669

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

In developing embryos, cells receive and interpret positional information as they become organized into discrete patterns and structures. One excellent model for understanding the genetic regulatory mechanisms that pattern cellular fields is the regulation and function of theachaete‐scutecomplex (AS‐C) in the developing nervous system of the fruit fly,Drosophila melanogaster.Three structurally homologous proneural genes—achaete (ac), scute (sc), andlethal of scute(l'sc)—are required for neural stem cell formation. InDrosophila, the AS‐C genes are initially expressed in patterns of cell clusters at reproducible anteroposterior (AP) and dorsoventral∗∗∗ (DV) coordinates that foreshadow where neural precursors arise. In the embryonic central nervous system (CNS), the gene products of AP and DV axis‐patterning genes act combinatorially via a large array of cis‐regulatory regions scattered throughout the AS‐C to generate a segmentally repeated pattern of proneural clusters. Within each cluster (an equivalence group), one cell then retains proneural gene expression and is singled out as the neural stem cell (neuroblast). The neuroblast inhibits the surrounding cells from adopting neural fates (lateral inhibition) through a signaling pathway that is mediated via the action of the proneural and neurogenic genes. The proneural genes therefore represent a nodal point in the patterning of the nervous system. They receive global positional information, transduce it to discrete sets of cells, and trigger local cell interactions that mediate cell fate decisions.— Skeath, J. B., Carroll, S. B. Theachaete‐scutecomplex: generation of cellular pattern and fate within theDrosophilanervous system.FASEB J.8: 714‐721; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050670

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Fundamental, yet unresolved, issues in developmental neurobiology concern the relative influence of genetic vs. epigenetic factors in determining cell phenotype and establishing positional relationships among clonally related cells in the developing and mature vertebrate central nervous system (CNS). Advances in our understanding of how cells acquire their identity awaited a means to introduce lineage tracers into dividing cells of the developing CNS where the progenitor cells, which are situated in a neuroepithelial layer adjacent to the ventricles, generally are small and inaccessible. The technique of retroviral‐mediated gene transfer, whereby a heritable, easily detectable marker such as the gene for lacZ is integrated into the DNA of individual progenitor cells, has been used to analyze the lineage relationships of cells in the CNS and to derive the types of progenitor cells in the proliferative zones at different developmental stages. Collectively, these studies indicate that the CNS uses more than one strategy to achieve cell diversity. The analysis of the phenotypic composition of the cells within a clone indicates that there are predominantly separate progenitor cells for each of the main cell types comprising the cerebral cortex by the onset of cortical neurogenesis, although in other systems mostly multipotential progenitor cells persist throughout neurogenesis. Here I will compare and contrast the inferred role of cell lineage in the developing cerebral cortex and olfactory bulb, where postmitotic neurons migrate relatively long distances from their site of generation to their final destination, with that in other regions of the CNS in which the displacement of postmitotic neurons from their birthplace is significantly less.— Luskin, M. B. Neuronal cell lineage in the vertebrate central nervous system.FASEB J.8: 722‐730; 1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050671

出版商:Wiley    

年代:1994

数据来源: WILEY

摘要:

Synaptogenesis can be analyzed in a simple array of motoneurons and muscle fibers of the embryos and larvae ofDrosophila melanogaster.Each abdominal hemisegment contains a stereotypic array of 30 muscle fibers. During middle to late embryogenesis, motoneurons exit the central nervous system to make precise synaptic connections with specific muscle fibers. Target recognition has been tested using both genetic and microsurgical manipulations, which indicate that motoneurons actively recognize specific muscle fibers. The molecular basis of target recognition has been examined by screens for mutations that disrupt both guidance events and correct innervation. In addition, the motoneurons and muscle fibers both express an array of putative cell adhesion molecules whose functions may contribute to normal connectivity. Postsynaptic specializations, including glutamate receptor distribution, depend on innervation and neural activity. The neuromuscular system is not “hardwired,” as motoneurons are capable of altering both their branch arborizations and connectivity in response to local denervation and blockade of synaptic function. Collectively, these studies show that theDrosophilamotor innervation is a powerful model system for testing at the cellular and molecular level the mechanisms that govern synaptic development.— Keshishian, H., Chang, T. N., Jarecki, J. Precision and plasticity duringDrosophilaneuromuscular development.FASEB J.8:731‐737;1994.

ISSN:0892-6638    

DOI:10.1096/fasebj.8.10.8050672

出版商:Wiley    

年代:1994

数据来源: WILEY