Adhesive and Signaling Functions of Cadherins and Catenins in Vertebrate Development

Properly regulated intercellular adhesion is critical for normal development of all metazoan organisms. Adherens junctions play an especially prominent role in development because they link the adhesive function of cadherin–catenin protein complexes to the dynamic forces of the actin cytoskeleton, which helps to orchestrate a spatially confined and very dynamic assembly of intercellular connections. Intriguingly, in addition to maintaining intercellular adhesion, cadherin–catenin proteins are linked to several major developmental signaling pathways crucial for normal morphogenesis. In this article we will highlight the key genetic studies that uncovered the role of cadherin–catenin proteins in vertebrate development and discuss the potential role of these proteins as molecular biosensors of external cellular microenvironment that may spatially confine signaling molecules and polarity cues to orchestrate cellular behavior throughout the complex process of normal morphogenesis.Development of any multicellular organism is impossible without a dynamic and properly regulated intercellular adhesion. Adhesive contacts between cells provide a physical anchoring system that is necessary to form highly organized tissues, and these contacts are essential for effective intercellular communication that ensures the homeostasis and survival of the entire organism. A number of unique developmental processes, including such early events as embryonic compaction and first cell fate specification, as well as later tissue morphogenesis and organogenesis, rely on a dynamic balance between cellular adhesion and migration. Cadherin–catenin protein complexes, which constitute the core of a specialized subtype of cellular adhesion structures termed adherens junctions (AJs), play a particularly important role during these processes. Apart from maintaining adhesive contacts at the cell–cell junctions, they are actively involved in epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions, which are crucial to sustain the tissue plasticity during development. Most importantly, the components of cadherin–catenin complexes are tightly linked to several major signaling networks controlling cell division, differentiation, and apoptosis and this feature is crucial for the broad roles of the AJs throughout the vertebrate development (see Cavey and Lecuit 2009).This article will focus on the role of cadherin–catenin proteins in regulating the signaling events critical for vertebrate development. Altering the expression pattern of particular cadherin–catenin complex components in the developing embryo often leads to major developmental defects, which reflect their role in both signaling and mechanical adhesion. In this article, we will highlight crucial findings suggesting that cadherin–catenin complexes provide not only the structural integrity of the tissue, but may also serve as biosensors of the external cellular microenvironment that modulate cellular behavior and make individual cells work together to ensure the fitness of the entire organism.     

Vertebrate sickness behaviors: Adaptive and integrated neuroendocrine immune responses

Vertebrate sickness behaviors, which include lethargy, anorexia, and decreased libido, can facilitate defense against pathogens by conserving energy for use in other immune responses and by limiting parasites' access to nutrients. Such benefits come with considerable costs, however, as lethargy decreases the time available for other fitness-enhancing activities and dampened libido directly reduces reproductive prospects. While the degree of sickness behaviors expressed varies among individuals, populations, and species, the ecological and physiological factors driving this diversity remain unclear. Here, we consider how an organism's ecological context and life-history strategy may impact the ways in which it balances the costs and benefits of sickness behaviors to enable or suppress its expression. Striking an appropriate balance requires physiological assimilation of information about external ecological conditions as well as about the status of infection and host nutrition. This integration requires multi-directional communication among the endocrine, nervous, and immune systems, the purview of the field of psychoneuroimmunology. This discipline portrays cytokines, signaling molecules originally characterized solely by their roles within the immune system, as key mediators of a brain-immune network that ensures the adaptive expression of sickness behaviors. Study of these molecules and the behaviors they coordinate in an ecological context will greatly augment our understanding of the natural variation in immune function found among wild animals.     

Tadpole Locomotion: Axial Movement and Tail Functions in a Largely Vertebraeless Vertebrate

SYNOPSIS.Tadpoles are exceptional among vertebrates in lackingvertebrae along most of their body axis. Their caudal myotomesare also unusually simple for free-living vertebrates. Thisoverall morphological simplicity, in theory, makes tadpolesgood models for exploring how vertebrates control undulatorymovements. We used electromyography (EMG), high speed ciné,computational fluid dynamics (CFD), and mechanical tissue testingto understand how Rana tadpoles regulate their locomotion. Bullfrog (Rana catesbeiana) tadpoles have several patterns ofmuscle activity, each specific to a particular swimming behavior.Ipsilateral muscles in the tail were active either in seriesor simultaneously, depending on the tadpole's velocity, andlinear and angular acceleration. When R. catesbeiana larvaeswam at their natural preferred tail beat frequency, musclesat the caudal end of their tail were inactive. Mechanical testsof tissue further suggest that the preferred tail beat frequencyclosely matches the resonance frequency of the tail thus minimizingthe energetic cost of locomotion. CFD modeling has demonstrated that the characteristically highamplitude oscillations at a tadpole's snout during normal rectilinearlocomotion do not add to drag, as might be supposed, but ratherhelp generate thrust. Mechanical testing of the tadpole tailfin has revealed that the fin is viscoelastic and stiffer insmall rather than large deformations. This property (among others)allows the tail to be light and flexible, yet stiff enough togenerate thrust in the absence of a bony or cartilaginous skeleton. Many recent studies have documented predator-induced polyphenismin tadpole tail shape. We suggest that this developmental plasticityin locomotor structures is more common in tadpoles than in othervertebrates because tadpoles do not need to reform skeletaltissue to change overall caudal shape. Tadpole tail fins and tip, in the absence of any skeleton, arefragile and often scarred by predators. Based on the high incidenceof tail fin injury seen in tadpoles in the wild, we suggestthat the tadpole tail fin and tip may play an ecological rolethat goes beyond serving as a propeller to help tadpoles staybeyond predators' reach. Those soft tissue axial structures,by failing under very small tensile loads, may also allow tadpolesto tear free of a predator's grasp.     

Molting of Rotylenchus buxophilus Golden

Molting of Rotylenchus buxophilus is similar in all observed post-embryonic stages. During molting the old cuticle and cephalic framework, conus of the old stylet, vestibulum extension, linings of amphids, distal part of the linings of the excretory duct, rectum, and phasmids are shed. The new styler is formed starting from the conus, which is simultaneously formed in its entirety.     

Physiological Control of Molting in Insects

SYNOPSIS. The initiation of a molting cycle in insects is neithera random nor a strictly periodic event. Insofar as molting canaccomplish different things under different circumstances, suchas a change in size or a change in form, it is reasonable toasume that the timing of a molt must be adapted to these functions.The onset of a metamorphic molt, in particular, must be preciselycontrolled because the onset of metamorphosis terminates thegrowth phase of a larva and establishes the body size of theadult insect. This aspect of the control of molting has receivedrelatively little attention and our knowledge of specific physiologicalmechanisms for the control of molt initiation is restrictedto three species: the blood-sucking bug, Rhodnius prolixus,the greater milkweed bug, Oncopeltus fasciatus, and the tobaccohornworm, Manduca sexta. The present review discusses the stateof our knowledge about the factors that render these insectscompetent to molt and about the stimuli that serve as a directtrigger for molting.     

Vertebrate pseudogenes

Pseudogenes are commonly encountered during investigation of the genomes of a wide range of life forms. This review concentrates on vertebrate, and in particular mammalian, pseudogenes and describes their origin and subsequent evolution. Consideration is also given to pseudogenes that are transcribed and to the unusual group of genes that exist at the interface between functional genes and non-functional pseudogenes. As the sequences of different genomes are characterised, the recognition and interpretation of pseudogene sequences will become more important and have a greater impact in the field of molecular genetics.     

Vertebrate mono-ADP-ribosyltransferases

Mono-ADP-ribosylation appears to be a reversible modification of proteins, which occurs in many eukaryotic and prokaryotic organisms. Multiple forms of arginine-specific ADP-ribosyltransferases have been purified and characterized from avian crythrocytes, chicken polymorphonuclear leukocytes and mammalian skeletal muscle. The avian transferases have similar molecular weights of28 kDa, but differ in physical, regulatory and kinetic properties and subcellular localization. Recently, a 38-kDa rabbit skeletal muscle ADP-ribosyltransferase was purified and cloned. The deduced amino acid sequence contained hydrophobic amino and carboxy termini, consistent with known signal sequences of glycosylphosphatidylinositol (GPI)-anchored proteins. This arginine-specific transferase was present on the surface of mouse myotubes and of NMU cells transfected with the cDNA and was released with phosphatidylinositol-specific phospholipase C. Arginine-specific ADP-ribosyltransferases thus appear to exhibit considerable diversity in their structure, cellular localization, regulation and physiological role.     

Hormonal Control of Molting in Decapod Crustacea

The involvement of the molting hormone, 20-hydroxyecdysone,in the mediation of molting in decapod crustaceans is brieflyreviewed. Aspects of the secretion and metabolism of its precursor,ecdysone, are discussed. Experiments are described that demonstratethe presence of a molt-inhibiting hormone (MIH) in the sinusglands of juvenile lobsters (Homarus americanus). Assays forMIH include measurement of the molt interval and radioimmunoassayof circulating titers of ecdysteroids in eyestalk-ablated lobsters.This latter assay indicates that sinus gland extracts significantlydecrease the concentration of circulating ecdysteroids 24 hrafter injection. Data are also presented on the circulatingtiters of ecdysteroids during multiple molt cycles of lobstersfollowing eyestalk ablation. These data indicate that theremust be another factor that ultimately regulates the circulatinglevels of the molting hormone.     

Vertebrate myotome development

The embryonic myotome generates both the axial musculature and the appendicular muscle of the fins and limbs. Early in embryo development the mesoderm is segmented into somites, and within these the primary myotome forms by a complex series of cellular movements and migrations. A new model of primary myotome formation in amniotes has emerged recently. The myotome also includes the muscle progenitor cells that are known to contribute to the secondary formation of the myotome. The adult myotome contains satellite cells that play an important role in adult muscle regeneration. Recent studies have shed light on how the growth and patterning of the myotome occurs.     

Vertebrate gastrulation.

Our understanding of the mechanisms that control gastrulation is still in its infancy. One problem is that gastrulation is a complex set of coordinated behaviours involving directional cell movements, several types of cell interactions, changes in cell fate and gene expression. Therefore, the successful analysis of its control mechanisms requires simultaneous analysis of more than one of these, or at least some way of separating them. Although progress has been slow, some recent studies have made significant advances in the field and we can probably look forward to some major breakthroughs in the near future.