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PubMed2001

Distinct signals generate repeating striped pattern in the embryonic parasegment.

How repeating striped patterns arise across cellular fields is unclear. To address this we examined the repeating pattern of Stripe (Sr) expression across the parasegment (PS) in Drosophila. This pattern is generated in two steps. First, the ligands Hedgehog (Hh) and Wingless (Wg) subdivide the PS into smaller territories. Second, the ligands Hh, Spitz (Spi), and Wg each emanate from a specific territory and induce Sr expression in an adjacent territory. We also show that the width of Sr expression is determined by signaling strength. Finally, an enhancer trap in the sr gene detects the response to Spi and Wg, but not to Hh, implying the existence of separable control elements in the sr gene. Thus, a distinct inductive event is used to initiate each element of the repeating striped pattern.

Animals↗

PubMed2002

Regulated proteolysis of Xom mediates dorsoventral pattern formation during early Xenopus development.

To identify a regulatory role for proteolysis during early Xenopus development, we developed a biochemical screen for proteins that are degraded in an embryonic stage-specific manner. We found that Xom, a homeobox transcriptional repressor of dorsal-specific genes, was degraded precipitously during early gastrulation. Xom degradation is regulated by phosphorylation at a GSK3-like consensus site and is most likely mediated by the SCF-beta-TRCP complex. Expression of nondegradable Xom represses transcription of dorsal genes much more effectively than wild-type Xom and results in a more strongly ventralized phenotype. We propose that regulated Xom proteolysis plays an essential role in the establishment of the dorsoventral axis, by converting a gradient in BMP abundance into a sharp dorsoventral pattern.

Animals↗

PubMed2000

Specificities of heparan sulphate proteoglycans in developmental processes.

Heparan sulphate proteoglycans are abundant cell-surface molecules that consist of a protein core to which heparan sulphate glycosaminoglycan chains are attached. The functions of these molecules have remained mostly underappreciated by developmental biologists; however, the actions of important signalling molecules, for example Wnt and Hedgehog, depend on them. To understand both the mechanisms by which ligands involved in development interact with their receptors and how morphogens pattern tissues, biologists need to consider the functions of heparan sulphate proteoglycans in signalling and developmental patterning.

Animals↗

PubMed2001

Multiple roles of EPH receptors and ephrins in neural development.

The control of cell movement during development is essential for forming and stabilizing the spatial organization of tissues and cell types. During initial steps of tissue patterning, distinct regional domains or cell types arise at appropriate locations, and the movement of cells is constrained in order to maintain spatial relationships during growth. In other situations, the guidance of migrating cells or neuronal growth cones to specific destinations underlies the establishment or remodeling of a pattern. Eph receptor tyrosine kinases and their ephrin ligands are key players in controlling these cell movements in many tissues and at multiple stages of patterning.

Animals↗

PubMed1998

Expression of the Hox gene complex in the indirect development of a sea urchin.

Hox complex genes control spatial patterning mechanisms in the development of arthropod and vertebrate body plans. Hox genes are all expressed during embryogenesis in these groups, which are all directly developing organisms in that embryogenesis leads at once to formation of major elements of the respective adult body plans. In the maximally indirect development of a large variety of invertebrates, the process of embryogenesis leads only to a free-living, bilaterally organized feeding larva. Maximal indirect development is exemplified in sea urchins. The 5-fold radially symmetric adult body plan of the sea urchin is generated long after embryogenesis is complete, by a separate process occurring within imaginal tissues set aside in the larva. The single Hox gene complex of Strongylocentrotus purpuratus contains 10 genes, and expression of eight of these genes was measured by quantitative methods during both embryonic and larval developmental stages and also in adult tissues. Only two of these genes are used significantly during the entire process of embryogenesis per se, although all are copiously expressed during the stages when the adult body plan is forming in the imaginal rudiment. They are also all expressed in various combinations in adult tissues. Thus, development of a microscopic, free-living organism of bilaterian grade, the larva, does not appear to require expression of the Hox gene cluster as such, whereas development of the adult body plan does. These observations reflect on mechanisms by which bilaterian metazoans might have arisen in Precambrian evolution.

Animals↗

PubMed1996

Body image concepts differ by age and sex in an Ojibway-Cree community in Canada.

Community-based studies of body image concepts can be useful for developing health interventions to prevent obesity-related diseases such as diabetes and cardiovascular disease in specific populations. First Nations peoples, in particular, face increased obesity-related health problems as a result of acculturative changes in diet and activity. This study examined body shape perception in an Ojibway-Cree community in Northern Ontario, Canada. A set of figure outline drawings ranging from very thin to very obese were used to examine perceived body shape, body shape satisfaction and ideals of healthiness across sex and age groups. Overall, only 16% of the population were satisfied with their current body shape. People with a higher body mass index (BMI) were less satisfied with their bodies and thought they were less healthy than people with a lower BMI. While females had a significantly greater BMI than males, males and females did not differ significantly in perception of current body shape. On the other hand, females desired relatively smaller body shapes than males (P < 0.05). Older people chose significantly larger healthy body shapes than did younger people (P < 0.05). Differences between our results and those reported for Anglo populations indicate that while both groups prefer body shapes smaller than those they have currently, the Ojibway-Cree tend to prefer relatively larger body shapes. Knowledge of age and sex-related patterns of body image concepts in communities can assist in the design of obesity-reducing interventions targeting specific groups.

Adolescent↗

PubMed2000

Alpha-synuclein inclusions in Alzheimer and Lewy body diseases.

Alpha-synuclein has assumed particular neuropathological interest in the light both of its identification as a non-beta-amyloid plaque constituent in Alzheimer disease (AD), and the recent association between dominant inheritance of Parkinson disease (PD) and 2 missense mutations at positions 30 and 53 of the synuclein protein. We report a systematic study of alpha-synuclein, tau, and ubiquitin immunoreactivity in representative neurodegenerative disorders of late life. The alpha-synuclein association with Lewy bodies is variable, peripheral, and is not stable with respect to proteases or acid treatment, whereas there is no association with Pick bodies. Stable patterns of immunoreactivity included neurites and a novel inclusion body. Although there is an overlap between the presence of Lewy bodies and stable alpha-synuclein immunoreactivity, this is seen only in the presence of concomitant neuropathological features of AD. The novel alpha-synuclein inclusion body identified in pyramidal cells of the medial temporal lobe in particular was found in AD and in the Lewy body variant of AD, and was associated neither with ubiquitin nor tau protein. The inclusion is therefore neither a Lewy body nor a PHF-core body, but may be confused with the Lewy body, particularly in the Lewy body variant of AD. Abnormal processing of alpha-synuclein leading to its deposition in the form of proteolytically stable deposits is a particular feature of the intermediate stages of AD.

Aged↗

PubMed1996

Patterning the vertebrate neuraxis.

Neuraxial patterning is a continuous process that extends over a protracted period of development. During gastrulation a crude anteroposterior pattern, detectable by molecular markers, is conferred on the neuroectoderm by signals from the endomesoderm that are largely inseparable from those of neural induction itself. This coarse-grained pattern is subsequently reinforced and refined by diverse, locally acting mechanisms. Segmentation and long-range signaling from organizing centers are prominent among the emerging principles governing regional pattern.

Animals↗

PubMed1996

Biomechanical analysis of the development of human bipedal walking by a neuro-musculo-skeletal model.

A new computer simulation method, using a neuro-musculo-skeletal model, is used to clarify the process of acquisition of erect bipedal walking during human ontogeny. Walking was autonomously generated as a dynamic interaction called 'mutual entrainment' between the neural oscillation and the pendular movement of differently proportioned bodies. Walking patterns of humans with 8 different sets of alternative body proportions, varying from those of 8-month-old children to those of 22 years old adults, were simulated. The development of bipedal walking is characterized as the change from a forced oscillation controlled by the nervous system to the natural oscillation of pendular motion, determined by body proportions. Body proportions are the fundamental factor in the development of bipedal walking.

Adult↗

PubMed1999

A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans.

We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes. Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures. Conversely, dbl-1 overexpression causes markedly increased body size and partly complementary male tail phenotypes, indicating that DBL-1 acts as a dose-dependent regulator of these processes. Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand. Our study of the dbl-1 expression pattern suggests a role for neuronal cells in global size regulation as well as male tail patterning.

Amino Acid Sequence↗

PubMed1995

Body composition in children with spastic quadriplegic cerebral palsy.

OBJECTIVE: To determine the pattern of body composition and nutritional status in a group of prepubertal children with spastic quadriplegic cerebral palsy (SQCP) compared with healthy control children. STUDY DESIGN: Subjects were enrolled for this cross-sectional study from two tertiary care settings. One hundred thirty-six subjects with SQCP, 2 to 12 years of age, were evaluated by anthropometric measures, or by anthropometric and total body water (TBW) measures (n = 28), with 39 control subjects. RESULTS: Body composition and nutritional status indicators were significantly reduced in children with SQCP. Accretion of fat-free mass with age was smaller for children with SQCP. Calculation of body fat from two skin folds correlated best with measures of fat mass from TBW. CONCLUSION: Malnutrition is common in children with SQCP. Clinically available, serial anthropometric measures enable the clinician to identify malnourished children with SQCP.

Age Factors↗

PubMed1984

Disorders of circadian body temperature rhythm in severely brain-damaged patients.

Twenty-four hour patterns of body temperature (BT) were recorded during consecutive 3-10 day spans from 14 severely brain-damaged patients. Seven patients exhibited a normal circadian BT rhythm with an amplitude of more than 1 degree C and a normal phase position of the minimum BT being observed during the latter half of the nocturnal sleep. One patient with a dispersed type of sleep exhibited an extremely low amplitude of the BT rhythm with mean average 0.69 degrees C. In this patient, an 24-hr observation span was insufficient to detect the existence of a BT rhythm. Two patients manifested disturbance of period. As acrophase of the BT rhythm varied from day to day, the standard deviation (S.D.) of mean acrophase was extremely large. For these patients the light-dark cycle did not act as an entrainer because both had visual disturbance. A phase advance of the minimum BT was observed in four patients. The minimum BT appeared in the first half of nocturnal sleep. These three disturbances (amplitude, period and phase), were revealed only by longitudinal observation of the BT rhythm, indicating the importance of long-term observations over a sufficient period to make the nature of the rhythm disturbances clear. These disturbances were not related to that of the sleep-wake cycle, as two patients showed normal circadian BT rhythm in spite of their dispersed-type sleep.

Activity Cycles↗

PubMed1996

Growth, growth hormone (GH)-binding protein, and GH receptors are differentially regulated by peak and trough components of the GH secretory pattern in the rat.

Body growth, GH secretory pattern, hepatic GH receptor (GHR), and plasma GH-binding protein (GHBP) levels are all sexually dimorphic in the rat. Male rats grow faster than females, and in GH-deficient animals, GH therapy is more effective when given in a pulsatile pattern rather than a continuous infusion. This contrasts with GHBP and hepatic GHR levels, which are lower in males than in females and raised by continuous but not pulsatile GH therapy. One possible explanation is that growth is primarily regulated by GH pulses, whereas GHR and GHBP are regulated mostly by the trough levels (which are lower in males than in females). To test this hypothesis directly, GH-deficient dwarf rats were given patterned iv infusions of hGH in which the relative contributions of the peak and trough components of the GH pattern were systematically varied, independently of dose, and their effects on weight and length gain, plasma GHBP, and hepatic GHR binding were measured. We found that the dose-response curves for GH given by pulsatile vs. continuous infusion were significantly nonparallel, and that growth was primarily stimulated by the pulsatile component of a mixed GH infusion pattern; doubling the GH dose by adding a continuous (c) infusion to a series of pulses (p) neither enhanced nor inhibited weight gain (36 micrograms hGH/day pulses (36p) vs. 36 micrograms hGH/day pulses + 36 micrograms hGH/day continuously (36p + 36c):0.9 +/- 0.2 g/day vs. 1.1 +/- 0.2 g/day), whereas doubling the GH dose by adding a pulsatile component significantly enhanced growth (72p:2.1 +/- 0.2 g/day, P < 0.01). Conversely, hepatic GHR and plasma GHBP levels were highly sensitive to the continuous element of the mixed infusion pattern and were totally unaffected by varying the pulsatile component over a wide range of doses. These results strongly suggest that growth and hepatic GHR/plasma GHBP respond differentially to the peak and trough components of the GH secretion pattern in the rat.

Animals↗

PubMed1999