Assembly and genetics of spore protective structures

The sporulation program in Bacillus subtilis ends in the formation of a highly resistant endospore that can withstand extremes of heat, mechanical disruption, ultraviolet irradiation, lytic enzymes and chemical attack. These properties are attributed mainly to the unique structure of spore coat and cortex, as well as to the physical state of the spore cytoplasm. The outermost layer of the spore, called the coat, has two morphologically distinct sublayers: an electron-dense outer coat and an electron-translucent inner coat. The coat is composed of more than 2 dozen proteins of varying size. Many coat genes and coat proteins have been isolated and characterized in detail, and studies of these have identified proteins with important roles in coat assembly, resistance and spore germination. We describe here characteristics of the coat proteins and propose a model for coat assembly based on recent work.     

Introduction: invertebrate axons find their way

The mechanisms that generate the immense complexity of synaptic connections within the developing nervous system have fascinated biologists for decades. Analysis of nervous system development in simple systems, such as insects, has made a major contribution to our understanding of the cellular and molecular mechanisms that control the formation of axon pathways and precise connections. This enterprise has a long, interesting, and somewhat controversial history. This collection of reviews on axon guidance in insects provides a brief update to integrate current molecular and developmental insights in a number of areas from initial axon pathfinding to the recognition of synaptic partners.     

The role of p53 in tumour suppression: lessons from mouse models

The use of mouse models has greatly contributed to our understanding of the role of p53 in tumour suppression. Mice homozygous for a deletion in the p53 gene develop tumours at high frequency, providing essential evidence for the importance of p53 as a tumour suppressor. Additionally, crossing these knockout mice or transgenic expression p53 dominant negative alleles with other tumour-prone mouse strains has allowed the effect of p53 loss on tumour development to be examined further. In a variety of mouse models, absence of p53 facilitates tumorigenesis, thus providing a means to study how the lack of p53 enhances tumour development and to define genetic pathways of p53 action. Depending on the particular model system, loss of p53 either results in deregulated cell-cylce entry or aberrant apoptosis (programmed cell death), confirming results found in cell culture systems and providing insight into in vitro function of p53. Finally, as p53 null mice rapidly develop tumours, they are useful for evaluating agents for either chemopreventative or therapeutic activities.     

Germline development in vertebrates and invertebrates

In all animals information is passed from parent to offspring via the germline, which segregates from the soma early in development and undergoes a complex developmental program to give rise to the adult gametes. Many aspects of germline development have been conserved throughout the animal kingdom. Here we review the unique properties of germ cells, the initial determination of germ cell fates, the maintenance of germ cell identity, the migration of germ cells to the somatic gonadal primordia and the proliferation of germ cells during development in vertebrates and invertebrates. Similarities in germline development in such diverse organisms as Drosophila melanogaster, Caenorhabditis elegans, Xenopus laevis and Mus musculus will be highlighted. Received 11 December 1998; received after revision 25 January 1999; accepted 25 January 1999     

The role of bHLH genes in ear development and evolution: revisiting a 10-year-old hypothesis

In mouse ear development, two bHLH genes, Atoh1 and Neurog1, are essential for hair cell and sensory neuron differentiation. Evolution converted the original simple atonal-dependent neurosensory cell formation program of diploblasts into the derived developmental program of vertebrates that generates two neurosensory cell types, the sensory neuron and the sensory hair cell. This transformation was achieved through gene multiplication in ancestral triploblasts resulting in the expansion of the atonal bHLH gene family. Novel genes of the Neurogenin and NeuroD families are upregulated prior to the expression of Atoh1. Recent data suggest that NeuroD and Neurogenin were lost or their function in neuronal specification reduced in flies, thus changing our perception of the evolution of these genes. This sequence of expression changes was accompanied by modification of the E-box binding sites of these genes to regulate different downstream genes and to form inhibitory loops among each other, thus fine-tuning expression transitions.     

Dual role of cAMP duringDictyostelium development

cAMP plays an essential role duringDictyostelium development both outside and inside the cell. Membrane-bound receptors and adenylyl cyclase are responsible for sensing and producing extracellular cAMP, whereas a phosphodiesterase is responsible for maintaining a low basal level. The molecular events underlying this type of hormone like signalling, which are now beginning to be deciphered, will be presented, in the light of cAMP analogue studies. The importance of intracellular cAMP for cell differentiation has been demonstrated by the central role of the cAMP dependent protein kinase. Mutants as well as strains obtained by reverse genetics will be reviewed which lead to our current understanding of the role of intracellular cAMP in the differentiation of both stalk and spore cells.     

Introduction: integrins, dynamic cell receptors

Integrins are a family of adhesive receptors consisting of α- and β-subunits which attach cells together via adhesive protein ligands or bind cells to extracellular matrix. They are found on virtually all cell types and link the external ligand to the cytoskeleton of the cell. Integrins also act as signal transducers both from the outside of the cell to the interior and also inside-out. Their main functions are in recognition and in tight but regulated binding. The series of reviews presented here cover both basic aspects of integrin function, including signal transduction, snake disintegrins and structure and function of I-domains in some integrin α-subunits, as well as the role of integrins in diseases, cancer, inflammation and cardiovascular diseases. The search for suitable inhibitors of integrins for treatment of these diseases and future prospects for their use are also discussed.     

Mechanisms of self-incompatibility in flowering plants

Self-incompatibility is a widespread mechanism in flowering plants that prevents inbreeding and promotes outcrossing. The self-incompatibility response is genetically controlled by one or more multi-allelic loci, and relies on a series of complex cellular interactions between the self-incompatible pollen and pistil. Although self-incompatibility functions ultimately to prevent self-fertilization, flowering plants have evolved several unique mechanisms for rejecting the self-incompatible pollen. The self-incompatibility system in the Solanaceae makes use of a multi-allelic RNase in the pistil to block incompatible pollen tube growth. In contrast, the Papaveraceae system appears to have complex cellular responses such as calcium fluxes, actin rearrangements, and programmed cell death occurring in the incompatible pollen tube. Finally, the Brassicaceae system has a receptor kinase signalling pathway activated in the pistil leading to pollen rejection. This review highlights the recent advances made towards understanding the cellular mechanisms involved in these self-incompatibility systems and discusses the striking differences between these systems. Received 10 May 2001; received after revision 20 June 2001; accepted 20 June 2001     

(In)discrete charm of the polyembryony: Evolution of embryo cloning

Polyembryonic development, where multiple embryos are formed from a single zygote, evolved at least 15 times in six different phyla in animals. The mechanisms leading to polyembryony and the forces that shaped the evolution of the polyembryonic developmental program have remained poorly understood. Recent studies of the polyembryonic development in the endoparasitic wasp Copidosoma floridanum have revealed that the evolution of polyembryony is associated with the evolution of developmental novelties such as total cleavage, early specification of embryonic and extra-embryonic fates, and a specific cell proliferation phase. These changes cumulatively result in the formation of thousands of embryos from a single egg. Laser ablation studies and analysis of early cell fate specification have revealed that a single blastomere representing the progenitor of the primordial germ cell regulates the proliferation of the embryos. We propose that evolutionary changes in cell cleavage, cell interactions, and the cell-differentiation program, reminiscent of interactions between the germinal stem cell and stem cell niche in fly ovaries, underlies the evolution of polyembryony. Received 30 January 2007; received after revision 21 June 2007; accepted 11 July 2007     

Soluble factors and the development of rod photoreceptors

Photoreceptors are the most abundant cell type in the vertebrate neural retina. Like the other retinal neurons and the Müller glia, they arise from a population of precursor cells that are multipotent and intrinsic to the retina. Approximately 10 years ago, several studies demonstrated that retinal precursor cells (RPCs) are competent to respond to environmental factors that promote cell type determination and differentiation. Since those studies, significant effort has been directed at identifying the molecular nature of these environmental signals and understanding the precise mechanisms they employ to drive RPCs towards the different retinal fates. In this review, we describe the recent progress toward understanding how environmental factors influence the development of vertebrate rod photoreceptors.     

Enteropathogenic Escherichia coli: a pathogen that inserts its own receptor into host cells

Enteropathogenic Escherichia coli (EPEC) is a major cause of infant diarrhea, killing hundreds of thousands of children per year worldwide. Intimate attachment to the host cell leading to the formation of actin-rich pedestals beneath the adhering bacteria is an essential feature of EPEC pathogenesis. EPEC attaches to host cells via the outer membrane adhesin, intimin. It was recently shown that EPEC inserts its own receptor for intimate adherence, Tir (translocated intimin receptor) into the host cell membrane. The focus of this review is on the discovery and characterization of this novel receptor, and our current understanding of its role in pedestal formation. Gram-negative bacterial secretion systems, including type III secretion systems, are reviewed and discussed in the context of Tir delivery into the host cell membrane. The relationship and relevance of in vitro models compared to the actual in vivo situation is essential to understanding disease. We have critically reviewed the use of animal models in studying EPEC infection. Elucidating the function of Tir will contribute to our understanding of how EPEC mediates disease.     

Spatiotemporal asymmetric auxin distribution: a means to coordinate plant development

The plant hormone auxin plays crucial roles in regulating plant growth development, including embryo and root patterning, organ formation, vascular tissue differentiation and growth responses to environmental stimuli. Asymmetric auxin distribution patterns have been observed within tissues, and these so-called auxin gradients change dynamically during different developmental processes. Most auxin is synthesized in the shoot and distributed directionally throughout the plant. This polar auxin transport is mediated by auxin influx and efflux facilitators, whose subcellular polar localizations guide the direction of auxin flow. The polar localization of PIN auxin efflux carriers changes in response to developmental and external cues in order to channel auxin flow in a regulated manner for organized growth. Auxin itself modulates the expression and subcellular localization of PIN proteins, contributing to a complex pattern of feedback regulation. Here we review the available information mainly from studies of a model plant, Arabidopsis thaliana, on the generation of auxin gradients, the regulation of polar auxin transport and further downstream cellular events. Received 10 March 2006; received after revision 26 June 2006; accepted 9 August 2006     

Modelling a ciliopathy: Ahi1 knockdown in model systems reveals an essential role in brain,retinal, and renal development

Joubert syndrome and related diseases (JSRD) are cerebello-oculo-renal syndromes with phenotypes including cerebellar hypoplasia, retinal dystrophy, and nephronophthisis (a cystic kidney disease). Mutations in AHI1 are the most common genetic cause of JSRD, with developmental hindbrain anomalies and retinal degeneration being prominent features. We demonstrate that Ahi1, a WD40 domain-containing protein, is highly conserved throughout evolution and its expression associates with ciliated organisms. In zebrafish ahi1 morphants, the phenotypic spectrum of JSRD is modeled, with embryos showing brain, eye, and ear abnormalities, together with renal cysts and cloacal dilatation. Following ahi1 knockdown in zebrafish, we demonstrate loss of cilia at Kupffer’s vesicle and subsequently defects in cardiac left–right asymmetry. Finally, using siRNA in renal epithelial cells we demonstrate a role for Ahi1 in both ciliogenesis and cell–cell junction formation. These data support a role for Ahi1 in epithelial cell organization and ciliary formation and explain the ciliopathy phenotype of AHI1 mutations in man.     

Cardiovascular development: towards biomedical applicability

Advances in our understanding of cardiac development have fuelled research into cellular approaches to myocardial repair of the damaged heart. In this collection of reviews we present recent advances into the basic mechanisms of heart development and the resident and non-resident progenitor cell populations that are currently being investigated as potential mediators of cardiac repair. Together these reviews illustrate that despite our current knowledge about how the heart is constructed, caution and much more research in this exciting field is essential. The current momentum to evaluate the potential for cardiac repair will in turn accelerate research into fundamental aspects of myocardial biology.     

Developmental genetics

Of particular concern to the human geneticist are the effects of genetic abnormalities on development. To gain an understanding of these effects it is necessary to engage in a reciprocal process of using knowledge of normal developmental events to elucidate the mechanisms operative in abnormal situations and then of using what is learned about these abnormal situations to expand our understanding of the normal. True developmental genes have not been described in man, although it is likely that they exist, but many developmental abnormalities are ascribable to mutations in genes coding for enzymes and structural proteins. Some of these even produce multiple malformation syndromes with dysmorphic features. These situations provide a precedent for asserting that not only monogenic developmental abnormalities, but also abnormalities resulting from chromosome imbalance must ultimately be explicable in molecular terms. However, the major problem confronted by the investigator interested in the pathogenesis of any of the chromosome anomaly syndromes is to understand how the presence of an extra set of normal genes or the loss of one of two sets of genes has an adverse effect on development. Several molecular mechanisms for which limited precedents exist may be considered on theoretical grounds. Because of the difficulties in studying developmental disorders in man, a variety of experimental systems have been employed. Particularly useful has been the mouse, which provides models for both monogenic and aneuploidy produced abnormalities of development. An example of the former is the mutation oligosyndactylism which in the heterozygous state causes oligosyndactyly and in the homozygous state causes early embryonic mitotic arrest. All whole arm trisomies and monosomies of the mouse can be produced experimentally, and of special interest is mouse trisomy 16 which has been developed as an animal model of human trisomy 21 (Down syndrome). In the long run, the most direct approach to elucidating the genetic problems of human development will involve not only the study of man himself but also of the appropriate experimental models in other species.