The spatial pattern and temporal sequence in which feather germs arise in the white Leghorn chick embryo

Feather germs arise in a specific sequence and spatio-temporal pattern within each of 10 feather areas on the White Leghorn chick embryo. The time of feather germ initiation was determined by histological and gross macroscopic analyses. Protruding feather germs are sequentially visualized in the dorsal, thigh, breast, head, humoral, ventral, wing, eye, and external auditory meatus feather areas, respectively, from stage 31- to stage 39+ [V. Hamburger and H.L. Hamilton (1951) J. Morphol. 88, 49-92]. The rate at which successive feather tracts appear was found to differ for different feather areas and was not simply due to the size of a feather area. Feather germ histogenesis was examined in the dorsal, thigh, breast, ventral, wing, and tail feather areas. The stages of feather germ histogenesis, examined on the wing feather area, are similar to those previously described for the dorsal surface. Gross and histological analyses gave different times and temporal sequences of feather germ visualization. Some feather areas were readily visualized at the time of feather germ initiation, while others showed a lag between the histological appearance of feather germs and their macroscopic visualization. Thus, macroscopic observations do not accurately reflect the pattern of histogenesis.     

The role of chick Ebf genes in the mediolateral patterning of the somites

This study was conducted to check whether the three chick Early B‐cell Factor (Ebf) genes, particularly cEbf1, would be targets for Shh and Bmp signals during somites mediolateral (ML) patterning. Tissue manipulations and gain and loss of function experiments for Shh and Bmp4 were performed and the results revealed that cEbf1 expression was initiated in the cranial presomitic mesoderm by low dose of Bmp4 from the lateral mesoderm and maintained in the ventromedial part of the epithelial somite and the medial sclerotome by Shh from the notochord; while cEbf2/3 expression was induced and maintained by Bmp4 and inhibited by high dose of Shh. To determine whether Ebf1 plays a role in somite patterning, transfection of a dominant‐negative construct was carried out; this showed suppression of cPax1 expression in the medial sclerotome and upregulation and medial expansion of cEbf3 and cPax3 expression in sclerotome and dermomyotome, respectively, suggesting that Ebf1 is important for ML patterning. Thus, it is possible that low doses of Bmp4 set up Ebf1 expression which, together with Shh from the notochord, leads to establishment of the medial sclerotome and suppression of lateral identities. These data also conclude that Bmp4 is required in both the medial and lateral domain of the somitic mesoderm to keep the ML identity of the sclerotome through maintenance of cEbf gene expression. These striking findings are novel and give a new insight on the role of Bmp4 on mediolateral patterning of somites.     

The spatial and temporal pattern of beta NGF receptor expression in the developing chick embryo

To gain insight into the developmental program of nerve growth factor (NGF) receptor expression, the binding of [125I] beta NGF to frozen chick sections was investigated autorradiographically between embryonic day 3 (E3) and post-hatching day 3. Strong NGF receptor expression was observed as early as E4, throughout embryonic development and in the post-hatching period at the classical NGF target sites: the paravertebral sensory and sympathetic ganglia, the paraaortal sympathetic ganglia as well as the cranial sensory ganglia with neurons of neural crest origin and their respective nerves. Only weak [125I] beta NGF binding was observed during a restricted time span in the parasympathetic ciliary ganglion. Clear differences were observed in the intensity and in the developmental time course of [125I] beta NGF binding to the dorsomedial and ventrolateral aspects of the dorsal root ganglia. NGF receptors were also found to be expressed on central axons of the dorsal root entry zone and the dorsal tract in the spinal cord. A transient expression of specific NGF binding sites of the same high affinity as measured at the classical NGF targets, was detected in the lateral motor column and in muscle at the time of motoneuron synapse formation and elimination.     

Storage of a temporal pattern sequence in a network

Learning of single patterns and a temporal pattern sequence in a network when the coupling coefficients between the network elements change their values according to a definite coupling function is described. In contrast to technical systems (e.g. film, tape) where temporal sequences are often encoded in the storage location, the network stores information only by changing the values of the coupling coefficients. A network of 100 elements was simulated on an UNIVAC 1100/80 computer. Eight single patterns and a sequence of these patterns were offered at the input of the network. After the learning process the network reproduces every stored pattern as an output signal when only parts of it are fed in. The activity, that is the sum of all output signals, is regulated by an external control signal. By setting that control signal to a suitable value the network is able to reproduce the stored pattern sequence starting from any arbitrary pattern. Lowering the external control signal during that process causes the network to hold the last presented pattern until the external control signal is changed again. It is speculated that the coupling function implemented in the simulation may be anaogous to a characteristic describing the chemical process of cooperative binding.Supported by DFG (Ha 381/9 and Ha 381/11)     

The spatial and temporal pattern of collagens I and II and keratan sulphate in the developing chick metatarsophalangeal joint

Both intrinsic and extrinsic factors are known to be involved in the morphogenesis of diarthrodial joints. The use of specific antibodies to collagens I and II and keratan-sulphate-containing proteoglycans (KSPG) has enabled the distributions of these macromolecules to be followed during the development of the third metatarsophalangeal joint in the chicken embryo. Our study shows that cartilage differentiation occurs as a continuous rod, which is then subsequently divided into separate elements. Further development also reveals that, unlike the matrix of the cartilaginous elements, there is a differential distribution of collagen (type II) and KSPG in the presumptive joint region. It is proposed that a decrease in KSPG in the presumptive joint region at stages 28/30 may be involved in the mechanism for the flattening of cells in formation of the interzone. Whereas, a decrease in collagen across the joint interzone region may provide an area of weakness, which might allow forces produced by the developing musculature to cause cavitation.     

Thoughts on the development, structure and evolution of the mammalian and avian telencephalic pallium

Various lines of evidence suggest that the development and evolution of the mammalian isocortex cannot be easily explained without an understanding of correlative changes in surrounding areas of the telencephalic pallium and subpallium. These are close neighbours in a common morphogenetic field and are postulated as sources of some cortical neuron types (and even of whole cortical areas). There is equal need to explain relevant developmental evolutionary changes in the dorsal thalamus, the major source of afferent inputs to the telencephalon (to both the pallium and subpallium). The mammalian isocortex evolved within an initially small dorsal part of the pallium of vertebrates, surrounded by other pallial parts, including some with a non-cortical, nuclear structure. Nuclear pallial elements are markedly voluminous in reptiles and birds, where they build the dorsal ventricular ridge, or hypopallium, which has been recently divided molecularly and structurally into a lateral pallium and a ventral pallium. Afferent pallial connections are often simplified as consisting of thalamic fibres that project either to focal cell aggregates in the ventral pallium (predominant in reptiles and birds) or to corticoid areas in the dorsal pallium (predominant in mammals). Karten's hypothesis, put forward in 1969, on the formation of some isocortical areas postulates an embryonic translocation into the nascent isocortex of the ventropallial thalamorecipient foci and respective downstream ventropallial target populations, as specific layer IV, layers II- III, or layers V-VI neuron populations. This view is considered critically in the light of various recent data, contrasting with the alternative possibility of a parallel, separate evolution of the different pallial parts. The new scenario reveals as well a separately evolving tiered structure of the dorsal thalamus, some of whose parts receive input from midbrain sensory centres (collothalamic nuclei), whereas other parts receive oligosynaptic 'lemniscal' connections bypassing the midbrain (lemnothalamic nuclei). An ampler look into known hodological patterns from this viewpoint suggests that ancient collothalamic pathways, which target ventropallial foci, are largely conserved in mammals, while some emergent cortical connections can be established by means of new collaterals in some of these pathways. The lemnothalamic pathways, which typically target ancestrally the dorsopallial isocortex, show parallel increments of relative size and structural diversification of both the thalamic cell populations and the cortical recipient areas. The evolving lemnothalamic pathways may interact developmentally with collothalamic corticopetal collaterals in the modality-specific invasion of the emergent new areas of isocortex.     

Acetyl-CoA drives the transcriptional growth program in yeast

Comment on: Cai L, et al. Mol Cell 2011; 42:426-37.     

The temporal pattern of feeding in the zebra finch

Feeding in zebra finches occurs in clearly defined bouts, but strong individual differences have been found in the finer details of its pattern. Some birds showed a constant probability of starting feeding with passage of time between meals and a constant probability of stopping during a meal. In these cases meal length (number of pecks at seed) tended to correlate with the length of the preceding gap. By contrast, in most individuals both meals and gaps tended to be of a typical length, and in some of these autocorrelation showed feeding to follow a cycle approximately 24 to 30 min long. Meal length in most of these birds correlated strongly with the length of the succeeding gap. The individual differences found are discussed and hypotheses put forward for their causation.     

Genetically identified neurons in avian auditory pallium mirror core principles of their mammalian counterparts

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The nucleotide sequence of the chick cytoplasmic beta-actin gene

The nucleotide sequence of the chick beta-actin gene was determined. The gene contains 5 introns; 4 interrupt the translated region at codons 41/42, 120/122, 267, 327/328 and a large intron occurs in the 5' untranslated region. The gene has a 97 nucleotide 5'-untranslated region and a 594 nucleotide 3'-untranslated region. A slight heterogeneity in the position of the poly A addition site exists; polyadenylation can occur at either of two positions two nucleotides apart. The gene codes for an mRNA of 1814 or 1816 nucleotides, excluding the poly(A) tail. In contrast to the chick skeletal muscle actin gene the beta-actin gene lacks the Cys codon between the initiator ATG and the codon for the N-terminal amino acid of the mature protein. In the 5' flanking DNA, 15 nucleotides downstream from the CCAAT sequence, is a tract of 25 nucleotides that is highly homologous to the sequence found in the same region of the rat beta-actin gene.     

Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) activation in temporal lobe epilepsy

Growing evidence from rodent models of temporal lobe epilepsy (TLE) indicates that dysregulation of the mammalian target of rapamycin (mTOR) pathway is involved in seizures and epileptogenesis. However, the role of the mTOR pathway in the epileptogenic process remains poorly understood. Here, we used an animal model of TLE and sclerotic hippocampus from patients with refractory TLE to determine whether cell-type specific activation of mTOR signaling occurs during each stage of epileptogenesis. In the TLE mouse model, we found that hyperactivation of the mTOR pathway is present in distinct hippocampal subfields at three different stages after kainate-induced seizures, and occurs in neurons of the granular and pyramidal cell layers, in reactive astrocytes, and in dispersed granule cells, respectively. In agreement with the findings in TLE mice, upregulated mTOR was observed in the sclerotic hippocampus of TLE patients. All sclerotic hippocampus (n = 13) exhibited widespread reactive astrocytes with overactivated mTOR, some of which invaded the dispersed granular layer. Moreover, two sclerotic hippocampus exhibited mTOR activation in some of the granule cells, which was accompanied by cell body hypertrophy. Taken together, our results indicate that mTOR activation is most prominent in reactive astrocytes in both an animal model of TLE and the sclerotic hippocampus from patients with drug resistant TLE.     

Studies on the mechanism of retinoid-induced pattern duplications in the early chick limb bud: temporal and spatial aspects

All-trans-retinoic acid causes striking digit pattern changes when it is continuously released from a bead implanted in the anterior margin of an early chick wing bud. In addition to the normal set of digits (234), extra digits form in a mirror-symmetrical arrangement, creating digit patterns such as a 432234. These retinoic acid-induced pattern duplications closely mimic those found after grafts of polarizing region cells to the same positions with regard to dose-response, timing, and positional effects. To elucidate the mechanism by which retinoic acid induces these pattern duplications, we have studied the temporal and spatial distribution of all-trans-retinoic acid and its potent analogue TTNPB in these limb buds. We find that the induction process is biphasic: there is an 8-h lag phase followed by a 6-h duplication phase, during which additional digits are irreversibly specified in the sequence digit 2, digit 3, digit 4. On average, formation of each digit seems to require between 1 and 2 h. The tissue concentrations, metabolic pattern, and spatial distribution of all- trans-retinoic acid and TTNPB in the limb rapidly reach a steady state, in which the continuous release of the retinoid is balanced by loss from metabolism and blood circulation. Pulse-chase experiments reveal that the half-time of clearance from the bud is 20 min for all-trans- retinoic acid and 80 min for TTNPB. Manipulations that change the experimentally induced steep concentration gradient of TTNPB suggest that a graded distribution of retinoid concentrations across the limb is required during the duplication phase to induce changes in the digit pattern. The extensive similarities between results obtained with retinoids and with polarizing region grafts raise the possibility that retinoic acid serves as a natural "morphogen" in the limb.     

Activation of cholecystokinin neurons in the dorsal pallium of the telencephalon is indispensable for the acquisition of chick imprinting behavior

Chick imprinting behavior is a good model for the study of learning and memory. Imprinting object is recognized and processed in the visual wulst, and the memory is stored in the intermediate medial mesopallium in the dorsal pallium of the telencephalon. We identified chicken cholecystokinin (CCK)-expressing cells localized in these area. The number of CCK mRNA-positive cells increased in chicks underwent imprinting training, and these cells expressed nuclear Fos immunoreactivity at high frequency in these regions. Most of these CCK-positive cells were glutamatergic and negative for parvalbumin immunoreactivity. Semi-quantitative PCR analysis revealed that the CCK mRNA levels were significantly increased in the trained chicks compared with untrained chicks. In contrast, the increase in CCK- and c-Fos-double-positive cells associated with the training was not observed after closure of the critical period. These results indicate that CCK cells in the dorsal pallium are activated acutely by visual training that can elicit imprinting. In addition, the CCK receptor antagonist significantly suppressed the acquisition of memory. These results suggest that the activation of CCK cells in the visual wulst as well as in the intermediate medial mesopallium by visual stimuli is indispensable for the acquisition of visual imprinting.     

The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma

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The role of pattern databases in sequence analysis

In the wake of the numerous now-fruitful genome projects, we are entering an era rich in biological data. The field of bioinformatics is poised to exploit this information in increasingly powerful ways, but the abundance and growing complexity both of the data and of the tools and resources required to analyse them are threatening to overwhelm us. Databases and their search tools are now an essential part of the research environment. However, the rate of sequence generation and the haphazard proliferation of databases have made it difficult to keep pace with developments. In an age of information overload, researchers want rapid, easy-to-use, reliable tools for functional characterisation of newly determined sequences. But what are those tools? How do we access them? Which should we use? This review focuses on a particular type of database that is increasingly used in the task of routine sequence analysis--the so-called pattern database. The paper aims to provide an overview of the current status of pattern databases in common use, outlining the methods behind them and giving pointers on their diagnostic strengths and weaknesses.     

The temporal pattern of vitellogenin synthesis in Drosophila grimshawi

The temporal pattern of protein production and, in particular, vitellogenin protein synthesis during the sexual maturation of Drosophila grimshawi females has been studied in vivo by briefly feeding the flies with 35S-methionine and 3H-amino acids. The overall level of incorporation was very low in young flies; it then progressively increased to reach a maximum with the onset of sexual maturity at 13-15 days. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses revealed three classes of proteins: those synthesized throughout the age spectrum, which constitute the majority of protein species; proteins synthesized primarily or only in young flies; and proteins synthesized only by the older flies. In this Drosophila species, the three vitellogenins (V1, V2, and V3) appeared to be synthesized in a two-phase pattern. In the first phase, small quantities of V1 and V2 were detected immunologically in the fat body and hemolymph of newly emerged and 1 day-old flies. These proteins did not accumulate in the hemolymph or the ovaries, apparently being unstable proteins. The second phase commenced in early vitellogenesis (7-9 days of age) with synthesis in the fat body of small quantities of V1 and V2, followed by V3 proteins. These proteins were secreted and accumulated in the hemolymph and 24 h later were found in the ovaries. Their quantities increased rapidly and a steady state of synthesis, release into the hemolymph, and uptake by the ovaries was reached by days 13-15. We have estimated that during the steady state of vitellogenin synthesis, a fly can synthesize in 24 h at least 152 micrograms of vitellogenins, which is more than 2% of its body weight, at an average rate of about 6.3 micrograms vitellogenins/h. About 2 micrograms of this are synthesized in the fat body, and about 4 micrograms in the ovaries. These findings are discussed in terms of their physiological implications and contrasted with the available data on Drosophila melanogaster.     

The AMA1-RON complex drives Plasmodium sporozoite invasion in the mosquito and mammalian hosts

Plasmodium sporozoites that are transmitted by blood-feeding female Anopheles mosquitoes invade hepatocytes for an initial round of intracellular replication, leading to the release of merozoites that invade and multiply within red blood cells. Sporozoites and merozoites share a number of proteins that are expressed by both stages, including the Apical Membrane Antigen 1 (AMA1) and the Rhoptry Neck Proteins (RONs). Although AMA1 and RONs are essential for merozoite invasion of erythrocytes during asexual blood stage replication of the parasite, their function in sporozoites was still unclear. Here we show that AMA1 interacts with RONs in mature sporozoites. By using DiCre-mediated conditional gene deletion in P. berghei, we demonstrate that loss of AMA1, RON2 or RON4 in sporozoites impairs colonization of the mosquito salivary glands and invasion of mammalian hepatocytes, without affecting transcellular parasite migration. Three-dimensional electron microscopy data showed that sporozoites enter salivary gland cells through a ring-like structure and by forming a transient vacuole. The absence of a functional AMA1-RON complex led to an altered morphology of the entry junction, associated with epithelial cell damage. Our data establish that AMA1 and RONs facilitate host cell invasion across Plasmodium invasive stages, and suggest that sporozoites use the AMA1-RON complex to efficiently and safely enter the mosquito salivary glands to ensure successful parasite transmission. These results open up the possibility of targeting the AMA1-RON complex for transmission-blocking antimalarial strategies.