Spatial distribution and developmental appearance of postjunctional P2X(1) receptors on smooth muscle cells of the mouse vas deferens

P2X(1)-type purinoceptors, have been shown to mediate fast transmission between sympathetic varicosities and smooth muscle cells in the mouse vas deferens but the spatial organization of these receptors on the smooth muscle cells remains inconclusive. Voltage clamp techniques were used to estimate the amplitudes of spontaneous excitatory junction currents (SEJCs) in cells of the vas deferens longitudinal smooth muscle layer. These currents involved the activation of about 6% of the P2X-type channels present on the cell, as compared to whole cell currents produced when isolated smooth muscle cells were exposed to maximal concentrations of either ATP or alpha,beta -MeATP. Immunofluorescence staining of the vas deferens with antibodies against P2X(1) receptor showed a diffuse, grainy distribution over the entire membrane of each smooth muscle cell. Anti-P2X(1) staining was not markedly clustered beneath anti-SV2-stained sympathetic varicosities. Similar results were obtained for cells in the urinary bladder. During development, P2X(1) mRNA was detected as early as embryonic day 15 (E15). Increasing intensities of diffuse immunostaining for P2X(1) were observed in the walls of the bladder, tail artery, and aorta from E15 until 6 weeks postnatal. The vas deferens showed increasing intensities of diffuse staining of its smooth muscle layers between 2 and 6 weeks postnatal, consistent with the time-course of development of fast purinergic transmission described previously. Together, the results suggest that the response of smooth muscle of the vas deferens to ATP released from sympathetic varicosities relies on rapidly desensitizing P2X(1) receptors, distributed diffusely across the smooth muscle cell surface. Synapse 42:1-11, 2001. (C) 2001 Wiley-Liss, Inc.

Developmental changes in hyperpolarization-activated currents I-h and I-K(IR) in isolated rat intracardiac neurons

The hyperpolarization-activated nonselective cation current, I-h, was investigated in neonatal and adult rat intracardiac neurons. I-h was observed in all neurons studied and displayed slow time-dependent rectification. I-h was isolated by blockade with external Cs+ (2 mM) and was inhibited irreversibly by the bradycardic agent, ZD 7288. Current density of I-h was approximately twofold greater in neurons from neonatal (-4.1 pA/pF at -130 mV) as compared with adult (-2.3 pA/pF) rats; however, the reversal potential and activation parameters were unchanged. The reversal potential and amplitude of I-h was sensitive to changes in external Na+ and K+ concentrations. An inwardly rectifying K+ current, I-K(IR), was also present in intracardiac neurons from adult but not neonatal rats and was blocked by extracellular Ba2+. I-K(IR) was present in approximately one-third of the adult intracardiac neurons studied, with a current density of -0.6 pA/pF at -130 mV. I-K(IR) displayed rapid activation kinetics and no time-dependent rectification consistent with the rapidly activating, inward K+ rectifier described in other mammalian autonomic neurons. I-K(IR) was sensitive to changes in external K+, whereby raising the external K+ concentration from 3 to 15 mM shifted the reversal potential by approximately +36 mV. Substitution of external Na+ had no effect on the reversal potential or amplitude of I-K(IR). I-K(IR) density increases as a function of postnatal development in a population of rat intracardiac neurons, which together with a concomitant decrease in I-h may contribute to changes in the modulation of neuronal excitability in adult versus neonatal rat intracardiac ganglia.

Signals from Eph and ephrin proteins: a developmental tool kit

Interactions between Eph receptors and their ligands the ephrin proteins are critically important in many key developmental processes. Emerging evidence also supports a role for these molecules in postembryonic tissues, particularly in pathological processes, including tissue injury and tumor metastasis. We review the signaling mechanisms that allow the 14 Eph and nine ephrin proteins to deliver intracellular signals that regulate cell shape and movement. What emerges is that the initiation of these signals is critically dependent on which Eph and ephrin proteins are expressed, the level of their expression, and, in some cases, which splice variants are expressed. Diversity at the level of initial interaction and in the downstream signaling processes regulated by Eph-ephrin signaling provides a subtle, versatile system of regulation of intercellular adhesion, cell shape, and cell motility.

Developmental genetics of red cell indices during puberty: A longitudinal twin study

Red cell number and size increase during puberty, particularly in males. The aim of the present study was to determine whether expression of genes affecting red cell indices varied with age and sex. Haemoglobin, red cell count, and mean cellular volume were measured longitudinally on 578 pairs of twins at twelve, fourteen and sixteen years of age. Data were analysed using a structural equation modeling approach, in which a variety of univariate and longitudinal simplex models were fitted to the data. Significant heritability was demonstrated for all variables across all ages. The genes involved did not differ between the sexes, although there was evidence for sex limitation in the case of haemoglobin at age twelve. Longitudinal analyses indicated that new genes affecting red cell indices were expressed at different stages of puberty. Some of these genes affected the different red cell indices pleiotropically, while others had effects specific to one variable only.

Developmental expression of a class IV POU gene in the gastropod Haliotis asinina supports a conserved role in sensory cell development in bilaterians

POU-IV genes regulate neuronal development in a number of deuterostomes (chordates) and ecdysozoans (arthropods and nematodes). Currently their function and expression in the third bilaterian clade, the Lophotrochozoa, comprising molluscs, annelids and. their affiliates, is unclear. Herein we characterise the developmental expression of HasPOU-IV in the gastropod mollusc, Haliotis asinina. The POU-IV gene is transiently expressed in I I distinct larval territories during the first 3 days of development. HasPOU-IV is first expressed in sets of ventral epidermal cells in the newly hatched trochophore larvae. As larval morphogenesis proceeds, we observe HasPOU-IV transcripts in cells that putatively form a range of sensory systems including chemo- and mechanosensory cells in the foot, cephalic tentacles, the ctenidia. the geosensory statocyst and the eyes. By comparing HasPOU-IV expression with POU-IV genes in other bilaterians we infer that this class of POU-domain genes had an ancestral role in regulating sensory cell development.

Evolution and developmental expression of nuclear receptor genes in the ascidian Herdmania

Nuclear receptors are a superfamily of metazoan transcription factors that have been shown to be involved in a wide range of developmental and physiological processes. A PCR-based survey of genomic DNA and developmental cDNAs from the ascidian Herdmania identifies eight members of this multigene family. Sequence comparisons and phylogenetic analyses reveal that these ascidian nuclear receptors are representative of five of the six previously defined nuclear receptor subfamilies and are apparent homologues of retinoic acid [NR1B], retinoid X [NR2B], peroxisome proliferator-activated [NR1C], estrogen related [NR3B], neuron-derived orphan (NOR) [NR4A3], nuclear orphan [NR4A], TR2 orphan [NR2C1] and COUP orphan [NR2F3] receptors. Phylogenetic analyses that include the ascidian genes produce topologically distinct trees that suggest a redefinition of some nuclear receptor subfamilies. These trees also suggest that extensive gene duplication occurred after the vertebrates split from invertebrate chordates. These ascidian nuclear receptor genes are expressed differentially during embryogenesis and metamorphosis.

The role of the Eph-ephrin signalling system in the regulation of developmental patterning

The Eph and ephrin system, consisting of fourteen Eph receptor tyrosine kinase proteins and nine ephrin membrane proteins in vertebrates, has been implicated in the regulation of many critical events during development. Binding of cell surface Eph and ephrin proteins results in bi-directional signals, which regulate the cytoskeletal, adhesive and motile properties of the interacting cells. Through these signals Eph and ephrin proteins are involved in early embryonic cell movements, which establish the germ layers, cell movements involved in formation of tissue boundaries and the pathfinding of axons. This review focuses on two vertebrate models, the zebrafish and mouse, in which experimental perturbation of Eph and/or ephrin expression in vivo have provided important insights into the role and functioning of the Eph/ephrin system.

Segmentation of spoken words into syllables by English-speaking children as compared to adults

Given the importance of syllables in the development of reading, spelling, and phonological awareness, information is needed about how children syllabify spoken words. To what extent is syllabification affected by knowledge of spelling, to what extent by phonology, and which phonological factors are influential? In Experiment 1, six- and seven-year-old children did not show effects of spelling on oral syllabification, performing similarly on words such as habit and rabbit. Spelling influenced the syllabification of older children and adults, with the results suggesting that knowledge of spelling must be well entrenched before it begins to affect oral syllabification. Experiment 2 revealed influences of phonological factors on syllabification that were similar across age groups. Young children, like older children and adults, showed differences between words with short and long vowels (e.g., lemon vs. demon) and words with sonorant and obstruent intervocalic consonants (e.g., melon vs. wagon). (C) 2002 Elsevier Science (USA). All rights reserved.

Applications of motion study in developmental disabilities: A review

Motion study is an engineering technology that analyzes human body motions. During the past decade (1990-1999) a series of studies investigated the role of motion study in developmental disabilities. This article reviews the literature on the applications of motion study in the field. A historical and conceptual review of motion study leading to the current status of studies is presented followed by a review of the research literature. Two main eras of research focus were identified. The first era (1990-1995) of studies established the superior effectiveness and efficiency of tasks designed with motion study or motion study-related principles over traditional site-based task designs. The second era (1995-1999) of studies examined the interaction between motion study-based task designs and other variables such as choice, preference, and functionally equivalent and competing task designs and communicative alternatives. Our review found that applying motion study principles as an antecedent guide and practice to eliminating or reducing ineffective motions and simplifying effective motions resulted in positive task outcomes with most of the participants.

Postural control and movement performance during upper limb tasks in children with developmental co-ordination disorder (DCD)

At least 6% of primary school aged children present with DCD, where co-ordination is substantially below the normal range for the child’s age and intelligence. Motor skill difficulties negatively affect academic achievement, recreation and activities of daily living. Poor upper-limb co-ordination is a common difficulty for children with DCD. A possible cause of this problem is deviant muscle timing in proximal muscle groups, which results in poor postural and movement control. While studies have been published investigating postural control in response to external perturbations, detail about postural muscle activity during voluntary movement is limited even in children with normal motor development. No studies have investigated the relationship between muscle timing, resultant arm motion and upper-limb coordination deficits. Objectives: To investigate the relationship between functional difficulties with upper-limb motor skills and neuromuscular components of postural stability and coordination. Specifically, to investigate onset-timing of muscle activity, timing of arm movement, and resultant three-dimensional (3D) arm co-ordination during rapid, voluntary arm movement and to analyse differences arising due to the presence of DCD. This study is part of a larger research program investigating postural stability and control of upper limb movement in children. Design: A controlled, cross-sectional study of differences between children with and without DCD. Methods: This study included 50 children aged eight to 10 years (25 with DCD and 25 without DCD). Children participated in assessment of motor skills according to the Movement ABC Test and a laboratory study of rapid, voluntary arm movements. Parameters investigated included muscle activation timing of shoulder and trunk muscles (surface electromyography), arm movement timing (light sensor) and resultant 3D arm motion (Fastrak). Results: A MANOVA is being used to analyse between-group differences. Preliminary results indicate children with DCD demonstrate altered muscle timing during a rapid arm raise when compared with the control group of children. Conclusion: Differences in proximal muscle timing in children with DCD support the hypothesis that altered proximal muscle activity may contribute to poor proximal stability and consequently poor arm movement control. This has implications for clinical physiotherapy.