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PubMed2006

The TGFbeta intracellular effector Smad3 regulates neuronal differentiation and cell fate specification in the developing spinal cord.

Here we show that Smad3, a transforming growth factor beta (TGFbeta)/activin signaling effector, is expressed in discrete progenitor domains along the dorsoventral axis of the developing chick spinal cord. Restriction of Smad3 expression to the dP6-p2 and p3 domains together with exclusion from the motoneuron progenitor domain, are the result of the activity of key transcription factors responsible for patterning the neural tube. Smad3-mediated TGFbeta activity promotes cell-cycle exit and neurogenesis by inhibiting the expression of Id proteins, and activating the expression of neurogenic factors and the cyclin-dependent-kinase-inhibitor p27(kip1). Furthermore, Smad3 activity induces differentiation of selected neuronal subtypes at the expense of other subtypes. Within the intermediate and ventral domains, Smad3 promotes differentiation of ventral interneurons at the expense of motoneuron generation. Consequently, the absence of Smad3 expression from the motoneuron progenitor domain during pattern formation of the neural tube is a prerequisite for the correct generation of spinal motoneurons.

Animals↗
PubMed1999

Ectodermal patterning in the avian embryo: epidermis versus neural plate.

Ectodermal patterning of the chick embryo begins in the uterus and continues during gastrulation, when cells with a neural fate become restricted to the neural plate around the primitive streak, and cells fated to become the epidermis to the periphery. The prospective epidermis at early stages is characterized by the expression of the homeobox gene DLX5, which remains an epidermal marker during gastrulation and neurulation. Later, some DLX5-expressing cells become internalized into the ventral forebrain and the neural crest at the hindbrain level. We studied the mechanism of ectodermal patterning by transplantation of Hensen's nodes and prechordal plates. The DLX5 marker indicates that not only a neural plate, but also a surrounding epidermis is induced in such operations. Similar effects can be obtained with neural plate grafts. These experiments demonstrate that the induction of a DLX5-positive epidermis is triggered by the midline, and the effect is transferred via the neural plate to the periphery. By repeated extirpations of the endoderm we suppressed the formation of an endoderm/mesoderm layer under the epiblast. This led to the generation of epidermis, and to the inhibition of neuroepithelium in the naked ectoderm. This suggests a signal necessary for neural, but inhibitory for epidermal development, normally coming from the lower layers. Finally, we demonstrate that BMP4, as well as BMP2, is capable of inducing epidermal fate by distorting the epidermis-neural plate boundary. This, however, does not happen independently within the neural plate or outside the normal DLX5 domain. In the area opaca, the co-transplantation of a BMP4 bead with a node graft leads to the induction of DLX5, thus indicating the cooperation of two factors. We conclude that ectodermal patterning is achieved by signalling both from the midline and from the periphery, within the upper but also from the lower layers.

Animals↗
PubMed2000

The morphogenetic role of midline mesendoderm and ectoderm in the development of the forebrain and the midbrain of the mouse embryo.

The anterior midline tissue (AML) of the late gastrula mouse embryo comprises the axial mesendoderm and the ventral neuroectoderm of the prospective forebrain, midbrain and rostral hindbrain. In this study, we have investigated the morphogenetic role of defined segments of the AML by testing their inductive and patterning activity and by assessing the impact of their ablation on the patterning of the neural tube at the early-somite-stage. Both rostral and caudal segments of the AML were found to induce neural gene activity in the host tissue; however, the de novo gene activity did not show any regional characteristic that might be correlated with the segmental origin of the AML. Removal of the rostral AML that contains the prechordal plate resulted in a truncation of the head accompanied by the loss of several forebrain markers. However, the remaining tissues reconstituted Gsc and Shh activity and expressed the ventral forebrain marker Nkx2.1. Furthermore, analysis of Gsc-deficient embryos reveals that the morphogenetic function of the rostral AML requires Gsc activity. Removal of the caudal AML led to a complete loss of midline molecular markers anterior to the 4th somite. In addition, Nkx2.1 expression was not detected in the ventral neural tube. The maintenance and function of the rostral AML therefore require inductive signals emanating from the caudal AML. Our results point to a role for AML in the refinement of the anteroposterior patterning and morphogenesis of the brain.

Animals↗
PubMed2002

Requirement of neuropilin 1-mediated Sema3A signals in patterning of the sympathetic nervous system.

Neuropilin 1 is the specific receptor for Sema3A and plays a role in nerve fiber guidance. We report that neuropilin 1 and Sema3A mutant mouse embryos, generated by targeted gene disruption, showed displacement of sympathetic neurons and their precursors and abnormal morphogenesis in the sympathetic trunk. We also show that Sema3A suppressed the cell migration activity of sympathetic neurons from wild-type but not neuropilin 1 mutant embryos in vitro and instead promoted their accumulation into compact cell masses and fasciculation of their neurites. These findings suggest that the neuropilin 1-mediated Sema3A signals regulate arrest and aggregation of sympathetic neuron precursors and sympathetic neurons themselves at defined target sites and axon fasciculation to produce the stereotyped sympathetic nerve pattern.

Animals↗
PubMedDate not supplied

[Comparative analysis of topological organization in Metazoa].

Topological patterns in Metazoa, using previously elaborated methodology with employment of the genus of the surface (p) as topological invariant are considered. The term "density of the genus of the surface" is introduced. In sponges and in a lesser degree among Cnidaria and, Ctenophoria an increase of genus p up to indefinite high values and the shaping of topologically complicated quasifractal systems (irrigation system in sponges and gastro-vascular system in Radiata) are evident. In most Bilateria a stable topological pattern with open digestive tube is formed and subsequent topological complications of other systems may occur. Complicated topological patterns increasing the genus of the surface are evolved on the base of quasifractal systems: gut pockets in turbellaria, tracheal system in arthropods, bronchial system in birds, gills in bivalve mollusks, etc. Peculiarities of ordered and disordered topological patterns as well as topological origin of the increase of the genus of the surface are considered.

Animals↗
PubMed2004

Geminin coordinates cell cycle and developmental control.

Growth and differentiation are two major themes in embryonic development. Numerous cell divisions have to be regulated on the path from a unicellular embryo, the zygote, to the multicellular structures of a mature being. Numerous functions, specializations and cellular identities have to be generated, in order to form a complex and mature animal. Numerous mechanisms have to control the correct assignment and acquisition of cellular fates, as well as the right timing and allocation of cells. Therefore, a strict coordination has to occur between embryonic patterning and the cell cycle. From this point of view, dual roles or mutual interactions of typical proliferation and developmental control genes are likely. Recently, new light was shed on these issues by identifying the nuclear protein Geminin as a molecular coordinator between the cell cycle and axial patterning. We summarize the role of Geminin in cell cycle, in the embryonic patterning controlled by Hox genes, providing insights into cell cycle regulators in embryonic development, and conversely, typical developmental control genes in cell cycle regulation.

Animals↗
PubMed1996

Pattern formation in the urodele mechanoreceptive lateral line: what features can be exploited for the study of development and evolution?

The lateral line is a specialized system of mechano- and electrosensory organs found in anamniotes. This system develops from ectodermal placodes, which migrate extensively along specific routes and deposit sensory organ anlagen at regular intervals, making it ideal for examining several important aspects of pattern formation. Urodele embryos are excellent model organisms for studies of pattern formation in the lateral-line system. The results of such studies are also important for understanding the evolutionary control of changes in pattern. The developmental mechanisms which control pattern formation in the urodele lateral line are reviewed, and some of the broader evolutionary implications of these mechanisms are discussed.

Ambystoma mexicanum↗
PubMed1999

Confirmation of pleisiomorphic daily torpor in mammals: the round-eared elephant shrew Macroscelides proboscideus (Macroscelidea).

The characteristics of daily torpor were measured in the round-eared elephant shrew Macroscelides proboscideus (Macroscelidea) in response to ambient temperature and food deprivation. Elephant shrews are an ancient mammal order within a superordinal African clade including hyraxes, elephants, dugongs and the aardvark. M. proboscideus only employed torpor when deprived of food; torpor did not occur under an ad libitum diet at ambient temperatures of 10, 15 and 25 degrees C. Torpor bout duration ranged from < 1 h to ca. 18 h. The times of entry into torpor were restricted to the scotophase, despite normothermic body temperature patterns indicating a rest phase coincident with the photophase. Full arousal was always achieved within the first 3 h of the photophase. When food deprived, the onset of the rest phase, and hence torpor, advanced with respect to the experimental photoperiod. The lowest torpor body temperature measured was 9.41 degrees C. Daily torpor in M. proboscideus confirms a pleisiomorphic origin of daily heterothermy. Torpor facilitates risk-averse foraging behaviour in these small omnivores by overcoming long-term energy shortfalls generated by the inherent variability of food availability in their semiarid, El Niño-afflicted habitats.

Adaptation, Physiological↗
PubMed2001

Reliability of individual differences in initial sensitivity and acute tolerance to nitrous oxide hypothermia.

On average, the hypothermia exhibited by rats receiving 60% nitrous oxide (N2O) eventually abates despite the continued inhalation of the drug (i.e., acute tolerance develops). However, large individual differences occur in both the magnitude of hypothermia achieved and the degree of acute tolerance that develops. To determine whether the degree of temperature loss and subsequent recovery during N2O administration are reliable characteristics of an individual, we measured intraperitoneal temperature via telemetry in 77 Long-Evans rats that each received 60% N2O for 5 h during two sessions separated by 14 days. Good intersession reliability (Pearson's r) was observed for simple change and adjusted change scores for both initial N2O temperature sensitivity (.61 < or = r < or = .62), and acute tolerance development (.46 < or = r < or = .52). In a separate experiment, three groups of rats were selected based on their individual body temperature patterns during an initial N2O administration: (1) insensitive to N2O hypothermia (n = 8); (2) marked hypothermia followed by acute tolerance development (n = 6); and (3) marked hypothermia followed by little acute tolerance development (n = 6). When retested 10 days later, each group exhibited a body temperature profile similar to that observed during the initial N2O exposure. Thus, the temperature profile observed during a rat's initial exposure to 60% N2O reflects a reproducible response for that animal.

Anesthetics, Inhalation↗
PubMedDate not supplied

[Body reaction at different periods to the action of a low-protein diet].

It has been shown in experiments on rats fed the diet with 7% protein that the body response pattern to the low protein content in food changes with time. During the first period, initial, rapidly occurring changes are passive in nature. The second period is marked by the development of an adaptive phase that is responsible for the maintenance of an adequate body homeostasis. During the third period that sets in if the duration of protein deficiency goes beyond the permissible limit, the body response is marked by the development of the deadaptation phase. It is assumed that the same changes are observed in children suffering from protein-caloric deficiency and that this fact should be taken into consideration in the management of the illness in question.

Absorption↗
PubMedDate not supplied

Effect of growth rate and body mass on resting metabolic rate in galliform chicks.

In this study, we asked whether within-species variation in chick resting metabolic rate was related to variation in growth and whether this relationship changed during development in three galliform species (turkey, Meleagris gallopavo, guinea fowl, Numida meleagris, and Japanese quail, Coturnix coturnix japonica). Resting metabolic rate increased by a bi- or triphasic pattern with body mass. For each phase, the relationship between metabolic rate and growth was studied by residual analysis, with two measures of growth: growth rate and body mass. Chick mass reflects the net result of accumulated growth, while hatchling mass reflects embryonic growth. In hatchlings, high metabolic rates coincided with low growth rates in turkeys and guinea fowl. These species delay initial food intake, and under these circumstances high metabolic expenditure may preclude conversion of yolk energy into body mass. No relationship was present between residual hatching metabolic rate and residual body mass. In older chicks, residual metabolic rate was positively linearly related with residual growth rate (turkeys and young quail) or residual body mass (guinea fowl and older quail). The similarity of the slopes suggests that growth rate and accumulated growth affected maintenance metabolism to the same extent throughout development. These findings suggest that growth models must take ontogenetic adjustments of metabolic rate into account in addition to costs of maintenance.

Aging↗
PubMed1994

STEPPING PATTERNS IN ANTS - INFLUENCE OF BODY MORPHOLOGY

The locomotory behaviour of 12 ant species belonging to four different genera (Formicinae: Cataglyphis, Formica, Lasius; Myrmicinae: Myrmica) was studied by filming individuals during walking on smoked-glass plates. Subsequent multivariate analyses of walking kinematics and footfall positions showed marked species-specific as well as size-dependent differences in the locomotory behaviour. The geometric properties of the footfall patterns resulting from the alternating tripod gait scale to leg dimensions in a geometric manner. At high speed, footprint distances between succeeding tripods exceed maximum leg extension, indicating that ants are 'trotting' from one tripod to the next one with intermittent aerial phases. In at least one species (Cataglyphis bombycina), there is evidence for quadrupedal locomotion at the highest speed. The functional relationship between stride length (s, the distance between successive footprints of the same foot) and speed (v) was best described by a curvilinear model, s=avb. Exponent b ranges from 0.3 to 0.6 and reveals differences between species. Within species, exponent b is constant, whereas factor a scales to leg length. Females and males show metachronal interleg coordination patterns rather than the alternating tripod coordination pattern seen in workers of the same species.

Journal Article↗
PubMed1998

Insulin resistance and fat patterning with aging: relationship to metabolic risk factors for cardiovascular disease.

Both insulin resistance and abdominal fat patterning are related to aging, and have been related to cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. However, previous studies have not used direct methods to quantify the independent strength of the association of each of these two putative primary factors with metabolic outcomes. We quantified overall obesity by the body mass index (BMI) and used a previously validated magnetic resonance imaging (MRI) method to quantify abdominal fat in 63 healthy nondiabetic individuals aged 22 to 83 years. We also measured the glucose and insulin response to an oral glucose tolerance test and the insulin sensitivity ([SI] by modified minimal model analysis). Body fat patterning was evaluated by the waist to hip ratio (WHR) and by MRI, which allowed direct measurement of subcutaneous (SCF) and intraabdominal (IAF) fat depots at the umbilicus in these subjects. These independent parameters were related to risk factors for CVD (blood pressure, lipids, and lipoproteins) and to plasma concentrations of free fatty acids (FFAs). Measures of overall obesity (BMI), total fat [TF], and/or SCF measured at the abdomen by MRI), glucose/insulin metabolism and SI, and central fat patterning (WHR or IAF measured by MRI) were correlated with mean arterial pressure (MAP), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) levels in univariate analysis and after controlling for age and gender. An index of central fat patterning (WHR) added to the informativeness of the insulin area under the curve (IAUC) in explaining 24% of the variability in plasma TG concentration, but measures of overall obesity were not independently related. Both the BMI and TF contributed to the IAUC in explaining 32% to 34% of the variability in MAP, but central fat patterning was not independently related. No index of overall obesity, fat patterning, glucose/insulin metabolism, and/or SI, was independently related to the plasma concentration of HDL-C after controlling for any one of the other two. Direct measurement of glucose/insulin metabolism and SI, as well as fat patterning, provides information on their relative associations with CVD risk factors. The measures of glucose/insulin metabolism and SI were more consistently related to dyslipidemia and hypertension than were the overall obesity and fat patterning in this healthy population.

Adipose Tissue↗
PubMed1991

The effect of exercise training on body weight and peptide hormone patterns in normal weight college-age men.

Resting and peak glucose, insulin, glucagon, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) levels were evaluated pretraining, 3 weeks and 10 weeks posttraining in seven college age males. The exercise consisted of thrice weekly session of jogging at 70% VO2max for 20 minutes plus warmup and cool down. Following the 10 weeks, VO2max increased significantly. Body weight remained constant and body fat decreased significantly. Fasting and peak blood glucose levels were normal at the beginning of the study yet improved with training. As expected, fasting and peak insulin levels decreased significantly with training. Although GIP did not change significantly with training, an uncoupling of GIP and insulin peak responses was observed. Glucagon levels were essentially unchanged. Fasting and peak PP levels increased slightly as training occurred. These hormone responses suggest that perhaps body weight and/or changes in body fat stores and fuel use might influence peptide hormone responses with training.

Adult↗
PubMed1997

The role of actin filaments in patterning the Caenorhabditis elegans cuticle.

Nematodes are covered by a cuticle with a prominent pattern of circumferentially oriented, parallel furrows. We report here that the pattern of furrows on the first larval cuticle of Caenorhabditis elegans, which is secreted during embryogenesis, is coincident with a pattern of submembranous actin filament bundles in the epithelial cells that secrete the cuticle. We propose that the pattern of cortical actin filaments biases the growth of the epithelial cell membranes, creating a furrowed surface template for deposition of the first cuticle layer. This layer then detaches from the epithelial cell surface as additional, nonpatterned components of the cuticle are secreted. Furrows are present on the surfaces of each of the four larval cuticles in C. elegans and on the adult cuticle. We show that similar ordered arrays of actin filaments appear during each of the postembryonic molts when new cuticles are synthesized. Our analysis suggests that conditions or mutations that affect the pattern of cuticle furrows might cause primary defects in the cytoskeletal organization of the epithelial cells that secrete the cuticle.

Actins↗
PubMed2000

glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development.

Glypicans represent a family of six cell surface heparan sulfate proteoglycans in vertebrates. Although no specific in vivo functions have thus far been described for these proteoglycans, spontaneous mutations in the human and induced deletions in the mouse glypican-3 (Gpc3) gene result in severe malformations and both pre- and postnatal overgrowth, known clinically as the Simpson-Golabi-Behmel syndrome (SGBS). Mice carrying mutant alleles of Gpc3 created by either targeted gene disruption or gene trapping display a wide range of phenotypes associated with SGBS including renal cystic dysplasia, ventral wall defects, and skeletal abnormalities that are consistent with the pattern of Gpc3 expression in the mouse embryo. Previous studies in Drosophila have implicated glypicans in the signaling of decapentaplegic, a BMP homolog. Our experiments with mice show a significant relationship between vertebrate BMP signaling and glypican function; GPC3-deficient animals were mated with mice haploinsufficient for bone morphogenetic protein-4 (Bmp4) and their offspring displayed a high penetrance of postaxial polydactyly and rib malformations not observed in either parent strain. This previously unknown link between glypican-3 and BMP4 function provides evidence of a role for glypicans in vertebrate limb patterning and skeletal development and suggests a mechanism for the skeletal defects seen in SGBS.

Animals↗
PubMed2004

A double segment periodicity underlies segment generation in centipede development.

The number of leg-bearing segments in centipedes varies extensively, between 15 and 191, and yet it is always odd. This suggests that segment generation in centipedes involves a stage with double segment periodicity and that evolutionary variation in segment number reflects the generation of these double segmental units. However, previous studies have revealed no trace of this. Here we report the expression of two genes, an odd-skipped related gene (odr1) and a caudal homolog, that serve as markers for early steps of segment formation in the geophilomorph centipede, Strigamia maritima. Dynamic expression of odr1 around the proctodaeum resolves into a series of concentric rings, revealing a pattern of double segment periodicity in overtly unsegmented tissue. Initially, the expression of the caudal homolog mirrors this double segment periodicity, but shortly before engrailed expression and overt segmentation, the intercalation of additional stripes generates a repeat with single segment periodicity. Our results provide the first clues about the causality of the unique and fascinating "all-odd" pattern of variation in centipede segment numbers and have implications for the evolution of the mechanisms of arthropod segmentation.

Animals↗
PubMed2005

FGF signaling is necessary for establishing gut tube domains along the anterior-posterior axis in vivo.

At the end of gastrulation in avians and mammals, the endoderm germ layer is an undetermined sheet of cells. Over the next 24-48 h, endoderm forms a primitive tube and becomes regionally specified along the anterior-posterior axis. Fgf4 is expressed in gastrulation and somite stage embryos in the vicinity of posterior endoderm that gives rise to the posterior gut. Moreover, the posterior endoderm adjacent to Fgf4-expressing mesoderm expresses the FGF-target genes Sprouty1 and 2 suggesting that endoderm respond to an FGF signal in vivo. Here, we report the first evidence suggesting that FGF4-mediated signaling is required for establishing gut tube domains along the A-P axis in vivo. At the gastrula stage, exposing endoderm to recombinant FGF4 protein results in an anterior shift in the Pdx1 and CdxB expression domains. These expression domains remain sensitive to FGF4 levels throughout early somite stages. Additionally, FGF4 represses the anterior endoderm markers Hex1 and Nkx2.1 and disrupts foregut morphogenesis. FGF signaling directly patterns endoderm and not via a secondary induction from another germ layer, as shown by expression of dominant-active FGFR1 specifically in endoderm, which results in ectopic anterior expression of Pdx1. Loss-of-function studies using the FGF receptor antagonist SU5402 demonstrate that FGF signaling is necessary for establishing midgut gene expression and for maintaining gene expression boundaries between the midgut and hindgut from gastrulation through somitogenesis. Moreover, FGF signaling in the primitive streak is necessary to restrict Hex1 expression to anterior endoderm. These data show that FGF signaling is critical for patterning the gut tube by promoting posterior and inhibiting anterior endoderm cell fate.

Animals↗