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PubMed1994

Lung development.

Human lung development is divided into five stages: embryonic, pseudoglandular, canalicular, saccular, and alveolar. The boundaries between these stages are not sharp; rather, overlap occurs between various gestational ages and individuals. The anatomic and morphological characteristics of each stage are described; general principles of lung development and cytodifferentiation of type I and type II pneumocytes are discussed. The complex phenomenon of lung development incorporates two processes--lung growth and lung maturation. Although these processes are developmentally related, they appear to be separately controlled. Lung growth seems to be influenced primarily by physical factors such as intrathoracic space, lung liquid volume and pressure, and amniotic fluid volume among others. Special attention is given to fetal lung liquid dynamics and the effects of its manipulation on lung growth, particularly by tracheal occlusion. Lung maturation has two components--structural and biochemical (ie, surfactant). Structural lung maturation appears to be regulated by physical factors. Physical factors that produce hypoplasia produce structurally immature lungs, whereas physical factors that produce hyperplasia produce structurally mature lungs. Biochemical maturation appears to be hormonally regulated by several endocrine organs (pituitary, adrenal, thyroid) and a host of endocrine factors including corticotropin, cortisol, thyroid hormones, and others.

Animals↗
PubMed1999

Precise developmental regulation of Ets family transcription factors during specification and commitment to the T cell lineage.

Ets family transcription factors control the expression of a large number of genes in hematopoietic cells. Here we show strikingly precise differential expression of a subset of these genes marking critical, early stages of mouse lymphocyte cell-type specification. Initially, the Ets family member factor Erg was identified during an arrayed cDNA library screen for genes encoding transcription factors expressed specifically during T cell lineage commitment. Multiparameter fluorescence-activated cell sorting for over a dozen cell surface markers was used to isolate 18 distinct primary-cell populations representing discrete T cell and B cell developmental stages, pluripotent lymphoid precursors, immature NK-like cells and myeloid hematopoietic cells. These populations were monitored for mRNA expression of the Erg, Ets-1, Ets-2, Fli-1, Tel, Elf-1, GABPalpha, PU.1 and Spi-B genes. The earliest stages in T cell differentiation show particularly dynamic Ets family gene regulation, with sharp transitions in expression correlating with specification and commitment events. Ets, Spi-B and PU.1 are expressed in these stages but not by later T-lineage cells. Erg is induced during T-lineage specification and then silenced permanently, after commitment, at the beta-selection checkpoint. Spi-B is transiently upregulated during commitment and then silenced at the same stage as Erg. T-lineage commitment itself is marked by repression of PU.1, a factor that regulates B-cell and myeloid genes. These results show that the set of Ets factors mobilized during T-lineage specification and commitment is different from the set that maintains T cell gene expression during thymocyte repertoire selection and in all classes of mature T cells.

Animals↗
PubMed2006

Maternal expression and function of the Drosophila sox gene Dichaete during oogenesis.

Members of the Sox family of DNA-binding HMG domain proteins have been shown to regulate gene transcription in a wide range of developmental processes, including sex determination, neurogenesis, and chondrogenesis. However, little is known about their potential functions in developing germline tissues. In Drosophila, the Sox protein Dichaete (a.k.a., Fish-hook) is a member of the SoxB subgroup whose HMG domain shares strong sequence similarity to that of vertebrate Sox2. Dichaete exhibits dynamic expression in embryonic and larval stages and has pleiotropic functions in a variety of tissues. In this study, we extend analyses of Dichaete function and show that expression of Dichaete protein is detected in the developing oocyte during early to mid stages of oogenesis. Strikingly, Dichaete exhibits cytoplasmic distribution and is not detected in the oocyte nucleus. Germline mosaic analyses revealed that the Dichaete gene has maternal functions that influence dorsal/ventral patterning of the egg chamber. Dichaete mutant eggs exhibit defects in formation of the dorsal appendages, differentiation of dorsal/anterior follicle cells, and mislocalization of Gurken protein and gurken mRNA. Dichaete protein was shown to possess RNA-binding capabilities, suggesting a direct post-transcriptional role in regulating RNA functions.

Animals↗
PubMed1996

Dynamics of vegetative cytoplasm during generative cell formation and pollen maturation in Arabidopsis thaliana.

Ultrastructural changes of pollen cytoplasm during generative cell formation and pollen maturation in Arabidopsis thaliana were studied. The pollen cytoplasm develops a complicated ultrastructure and changes dramatically during these stages. Lipid droplets increase after generative cell formation and their organization and distribution change with the developmental stage. Starch grains in amyloplasts increase in number and size during generative and sperm cell formation and decrease at pollen maturity. The shape and membrane system of mitochondria change only slightly. Dictyosomes become very prominent, and numerous associated vesicles are observed during and after sperm cell formation. Endoplasmic reticulum appears extensively as stacks during sperm cell formation. Free and polyribosomes are abundant in the cytoplasm at all developmental stages although they appear denser at certain stages and in some areas. In mature pollen, all organelles are randomly distributed throughout the vegetative cytoplasm and numerous small particles appear. Organization and distribution of storage substances and appearance of these small particles during generative and sperm cell formation and pollen maturation are discussed.

Arabidopsis↗
PubMed1994

Developmental changes in nerve growth factor (NGF) binding and NGF receptor proteins trkA and p75 in the facial nerve.

This study characterizes the temporal-spatial distribution of nerve growth factor (NGF) low (p75) and high-affinity (trkA) receptors in the facial nerve and geniculate ganglion (GG) of developing quail embryos (E-3 to E-14). We used 125I-labeled NGF (125I-NGF) to study binding dynamics in a temporal series of isolated primordia and an autoradiographic series of staged specimens to characterize the occurrence and distribution of NGF receptors in this cranial nerve and its ganglion. In addition, expression of trkA and p75 protein-like immunoreactivity in the facial nerve and GG was studied by Western blot, in order to distinguish between high- and low-affinity NGF receptors respectively. The quantitative study of binding show that isolated facial primordia ranging from E-3 to E-14 exhibit different levels of specific binding. High initial binding levels were observed on E-3 specimens, then an initial decrease on day 4 (E-4) followed by a steady increase from days E-4 to E-7. Maximum 125I-NGF binding was achieved on E-7, followed by a steady decline in binding on days 8 (E-8) and 9 (E-9), reaching near background levels on day 10 (E-10) of development and until the oldest stage assayed (E-14). Most of the cells bearing NGF receptors appeared to be non-neuronal crest-derived cells, but some placode-derived neurons and motor fibers of the VIIth cranial nerve transiently expressed the ability to bind 125I-NGF. The temporal pattern of p75 expression matches the pattern of quantitative binding of NGF, while the trkA expression is restricted to a few stages mainly E7 and E9, implying that most of the binding detected is via low-affinity receptors, except for a proportion of high-affinity receptors present at stages of maximum binding. This temporal pattern of NGF binding sites suggests that cells within the VIIth cranial nerve are responsive to and/or dependent upon NGF in vivo, so NGF may play a biological role during normal development of the facial nerve. In view of the developmental events that parallel the occurrence and type of NGF binding sites, we suggest that this role may be to modulate from earlier chemotaxis and cell proliferation to much later events, such as neuronal differentiation and neuron-glia interactions. The significance of these findings in regeneration during adult life remain to be investigated.

Animals↗
PubMed1998

G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at gastrulation and dynamic expression during neurulation.

Gastrulation in rodents is associated with an increase in the rate of growth and with the start of differentiation within the embryo proper. In an effort to understand the role played by the cell cycle control in these processes, expression of cyclin D1, D2, and D3--three major positive regulators of the G1/S transition--has been investigated by in situ hybrization and RT-PCR. Cyclin D1 and D2 transcripts are first detected in the epiblast at gastrulation, when a proliferative burst occurs, and subsequently in its differentiated derivatives within the embryo proper, indicating that activation of their expression takes place prior to the differentiation of epiblast progenitors. In contrast, cyclin D3 transcript is undetectable in the epiblast itself and its expression is activated exclusively in extraembryonic tissues of both epiblast and trophoblast origin. During neurulation, expression of each cyclin D RNA is dynamically regulated along the anterior-posterior axis. In the hindbrain, cyclin D1 and D2 show distinct segment-specific restricted expression and this pattern is conserved between mouse and chick. These results strongly suggest that D-type cyclins act as developmental regulators.

Animals↗
PubMed2006

Flexible flatfoot and related factors in primary school children: a report of a screening study.

The aim of this study was to analyze the longitudinal arch morphology and related factors in primary school children. Five hundred and seventy-nine primary school children were enrolled in the study. Generalized joint laxity, foot progression angle, frontal hindfoot alignment, and longitudinal arch height in dynamic position were evaluated. The footprints were recorded by Harris and Beath footprint mat and arch index of Staheli was calculated. The mean age was 9.23 +/- 1.66 years. Four hundred and fifty-six children (82.8%) were evaluated as normal and mild flexible flatfoot, and 95 children (17.2%) were evaluated as moderate and severe flexible flatfoot. The mean arch indices of the feet was 0.74 +/- 0.25. The percentage of flexible flatfoot in hypermobile and non-hypermobile children was found 27.6 and 13.4%, respectively. There was a statistically significant difference in dynamic arch evaluation between hypermobile and non-hypermobile children. There was a significant negative correlation between arch index and age, and a significant negative correlation between hypermobility score and age. Our study confirms that the flexible flatfoot and the hypermobility are developmental profiles.

Age Factors↗
PubMed2003

Developmental changes in the ploidy of mouse implanting trophoblast cells in vitro.

Shortly after the onset of implantation, polar mouse trophoblast cells proliferate and give rise to the ectoplacental cone, constituted by two distinct cell populations: undifferentiated, diploid cells and giant cells. Giant cells characteristically exhibit exaggerated dimensions and polyploid nuclei. In this study, we employ ectoplacental cones as a dynamic source of trophoblast giant cells to analyze cell proliferation, cell death, and ploidy under in vitro conditions. Our results show that DNA synthesis and the increase in the cell number are relevant only during the first 24 h of culture. Subsequently, DNA synthesis still occurs, mainly in the giant cell compartment, while the number of cells gradually decreases. Cell death by injury and apoptosis was also observed in the non-giant cell compartment of the ectoplacental cone. These findings suggest that the first 24 h of culture are crucial to the mitotic activity of the ectoplacental cone cells that gradually ceases, favoring the endoreduplication process. The DNA synthesis index during the subsequent experimental intervals emphasizes accumulation of DNA for the polyploidization. There was clear correlation between DNA content and nuclear dimension. The ploidy values for the trophoblast giant cells varied from 2C up to 368C in the giant cells, but were not as expressive as those known from in vivo conditions, probably due to the absence of regulatory factors specific to the embryonic-maternal interface. In situ hybridization and histochemistry for the nucleolus-organizing region showed that trophoblast nuclei have only two marker signals, indicative of a typical polytenic process. This present study elucidates important aspects of trophoblast behavior and provides new information on trophoblast physiology in vivo and in vitro.

Animals↗
PubMed2005

Expression of chemokine receptor CXCR4 during chick embryo development.

The chemokine receptor CXCR4 plays a decisive role in physiological cell migration both in developmental processes and adult tissues; it has also been implicated in metastasis formation of different human cancers (Balkwill 2004) and in HIV pathogenesis (Murdoch 2000). Here we present the expression pattern of this important chemokine receptor CXCR4 in the chick embryo. A dynamic expression pattern can be detected beginning as early as the gastrulation stages until the observed stage of HH28. During gastrulation, expression was observed in the epiblast at the level of the primitive streak and in the endoderm. Later, expression was noticeable in the ventral foregut portal, developing somites, tail bud, neural tube, the intermediate mesoderm, Wolffian duct, the lateral plate mesoderm and the developing blood vessels. Our descriptive data suggest a role for CXCR4 in gastrulation and other morphogenetic events connected with angiogenesis and kidney development.

Animals↗
PubMed1985

Commitment in a murine embryonal carcinoma cell line during differentiation induced by retinoic acid.

Murine embryonal carcinoma (EC) cells are induced to differentiate when cultured in the presence of retinoic acid (RA). Whereas the EC cells have a high plating efficiency, the differentiated cells have little or no colony-forming ability under the same conditions. We have assumed that the loss of colony-forming ability following exposure of EC cells to RA corresponds to the irreversible commitment of EC cells to differentiate. We found that uncommitted EC cells persist in RA-treated aggregates of EC cells and that the proportion of EC cells stabilizes at a level inversely related to the RA concentration. Both experimental evidence and mathematical modelling results are consistent with the interpretation that there is a dynamic equilibrium achieved by a balance between the processes of EC cell proliferation and differentiation. Since different cell types are induced by different RA concentrations, our results suggest that the commitment to differentiate is not related in any simple way to the developmental program which ensues.

Animals↗
PubMed2005

RhoA acts downstream of Wnt5 and Wnt11 to regulate convergence and extension movements by involving effectors Rho kinase and Diaphanous: use of zebrafish as an in vivo model for GTPase signaling.

Gastrulation shapes the early embryos by forming three germ layers, ectoderm, mesoderm and endoderm. In vertebrates, this process requires massive cell rearrangement including convergence and extension (CE) movements that involve narrowing and lengthening of embryonic tissues as well as cell elongation. Such polarization and movements require precise reorganization and regulation of the cytoskeleton network and cell adhesion. Rho small GTPases are key regulators for dynamic actin cytoskeleton. However, the signaling mechanisms underlying their functions in CE remain to be further elucidated. We have cloned the zebrafish Danio rerio rhoA and by capitalizing on the specific functional knockdown using morpholinos against rhoA and the availability of CE mutants defective in Wnt signaling, we showed that rhoA morphants were reminiscent to noncanonical wnt mutants with serious disruption in CE movements. Injection of rhoA mRNA effectively rescued such defects in wnt5 and wnt11 mutants. Furthermore, CE defects in rhoA knockdown or wnt mutants can be suppressed through functional bypass after ectopic expression of the two mammalian Rho effectors, the Rho kinase and Diaphanous (mDia). These results provide the first evidence that the RhoA in vivo acts downstream of Wnt5 and Wnt11 to effect, without affecting cell fates, on the CE movements in zebrafish embryos. Significantly, it elicits such effect via both effectors, Rho kinase and Dia. These findings also support the versatility of the zebrafish as a model to further investigate the roles of various classes of small GTPases in regulating cell dynamics in vivo.

Amino Acid Sequence↗
PubMed2004

Death in the third dimension: apoptosis regulation and tissue architecture.

Tissue development, homeostasis and tumor pathogenesis all depend upon a complex dialogue between multiple cell types operating within a dynamic three-dimensional (3D) tissue extracellular matrix microenvironment. A major issue is whether the spatial organization of a cell within this 3D tissue microenvironment could modulate cell responsiveness to regulate cell fate decisions such as survival, and if so how. Classic developmental model systems and transgenic animals are instructive but pose special challenges for investigators conducting signaling studies and biochemical assays in tissues. As an alternative, 3D culture model systems exist in which cell-adhesion dependent tissue architecture, heterotypic cell-cell interactions and tissue differentiation can be recapitulated with good fidelity. 3D cell culture models are slowly revealing how tissue architecture can dramatically influence how a cell responds to exogenous stimuli to modify its apoptotic behavior and hence should prove instrumental for identifying novel cell death pathways.

Apoptosis↗
PubMed2000

dtrap-1 encodes a novel member of the heat shock super family of proteins and is expressed in derivatives of all three germ layers during Drosophila embryogenesis.

Heat shock proteins (Hsps) comprise a highly conserved superfamily of proteins that are required for stress tolerance in living cells. At physiological conditions, these proteins act as chaperones during protein folding and protein assembly processes (Parsell and Lindquist, 1993. Annu. Rev. Genet. 27, 427-496). Members of the subfamily of Hsp90 proteins were shown to be additionally involved in the presentation and structural modification of components of diverse cellular signal transduction pathways including steroid hormone reception and regulatory kinase activities (Pratt, 1993. J. Biol. Chem. 268, 21455-21458); Cutforth et al., 1994. Cell 77, 1027-1036; van der Straten et al., 1997. EMBO J. 16, 1961-1997; Hunter and Poon, 1997. Trends Cell Biol. 7, 157-161). We have identified a Drosophila gene, called dtrap-1, which encodes a Hsp of a novel subfamily that is related to the Hsp90 family of proteins. During oogenesis dtrap-1 is expressed in nurse cells and its transcripts accumulate in the oocyte. The maternal transcripts remain in the egg but rapidly degrade during early embryogenesis, except in the posterior pole region. Zygotic expression is initiated after the onset of gastrulation showing dynamic patterns of transcripts in the developing mid- and hindgut as well as a subset of mesoderm derivatives.

Animals↗
PubMed2006

Transcription in four dimensions: nuclear receptor-directed initiation of gene expression.

Regulated gene expression, achieved through the coordinated assembly of transcription factors, co-regulators and the basal transcription machinery on promoters, is an initial step in accomplishing cell specificity and homeostasis. Traditional models of transcriptional regulation tend to be static, although gene expression profiles change with time to adapt to developmental and environmental cues. Furthermore, biochemical and structural studies have determined that initiation of transcription progresses through a series of ordered events. By integrating time into the analysis of transcription, chromatin immunoprecipitation assays and live-cell imaging techniques have revealed the dynamic, cooperative, functionally redundant and cyclical nature of gene expression. In this review, we present a dynamic model of gene transcription that integrates data obtained by these two techniques.

Animals↗
PubMed2006

DNA methylation-dependent epigenetic regulation of dimethylarginine dimethylaminohydrolase 2 gene in trophoblast cell lineage.

Trophoblast cell lineage is established through the first cellular differentiation in mammalian embryogenesis, and its developmental potential is restricted to the extraembryonic tissues contributing solely to the placenta. Several lines of evidence suggest a relative lack of importance of DNA methylation in gene regulation in the extraembryonic tissues when compared with embryonic ones. Here we analyzed the dynamics of epigenetic status in the upstream region of mouse Ddah2 gene, which was found to be specifically repressed in a stem cell population of trophoblast cell lineage. We found a tissue-dependent differentially methylated region in the regulatory region of the Ddah2 gene. This region was hypermethylated in trophoblast stem cells and was hypomethylated in differentiated cells both in vivo and in vitro. This change was well correlated with Ddah2 expression. In addition, in vitro methylation confined to the differentially methylated region was sufficient to repress promoter activity in the reporter assay. Furthermore, a repressive pattern of histone modifications was formed around the differentially methylated region in undifferentiated trophoblast stem cells with repressed Ddah2. Our data suggest that DNA methylation-mediated chromatin remodeling is involved in the regulation of the Ddah2 gene expression and thus is important even in trophoblast cell lineage.

Amidohydrolases↗
PubMedDate not supplied

A method for determining the dynamics and intensity of average growth.

A new statistical method is presented for determining an average growth curve which is valid in the sense of representing both the average dynamic, or tempo, and the average intensity of the growth process studied. In this context, growth curve means either distance, velocity or acceleration curve. The principal idea is to shift individual curves continuously (and non-linearly) in age to an average developmental age scale. Since the resulting curves represent the typical shape rather than individual variations of it, they are of interest for comparisons of different variables of boys and girls and of subgroups. The method is illustrated with longitudinal growth data from the first Zurich longitudinal study.

Body Height↗
PubMed2005

Green sperm. Identification of male gamete promoters in Arabidopsis.

Previously, in an effort to better understand the male contribution to fertilization, we completed a maize (Zea mays) sperm expressed sequence tag project. Here, we used this resource to identify promoters that would direct gene expression in sperm cells. We used reverse transcription-polymerase chain reaction to identify probable sperm-specific transcripts in maize and then identified their best sequence matches in the Arabidopsis (Arabidopsis thaliana) genome. We tested five different Arabidopsis promoters for cell specificity, using an enhanced green fluorescent protein reporter gene. In pollen, the AtGEX1 (At5g55490) promoter is active in the sperm cells and not in the progenitor generative cell or in the vegetative cell, but it is also active in ovules, roots, and guard cells. The AtGEX2 (At5g49150) promoter is active only in the sperm cells and in the progenitor generative cell, but not in the vegetative cell or in other tissues. A third promoter, AtVEX1 (At5g62850) [corrected] was active in the vegetative cell during the later stages of pollen development; the other promoters tested (At1g66770 and At1g73350) did not function in pollen. Comparisons among GEX1 and GEX2 homologs from maize, rice (Oryza sativa), Arabidopsis, and poplar (Populus trichocarpa) revealed a core binding site for Dof transcription factors. The AtGEX1 and AtGEX2 promoters will be useful for manipulating gene expression in sperm cells, for localization and functional analyses of sperm proteins, and for imaging of sperm dynamics as they are transported in the pollen tube to the embryo sac.

Arabidopsis↗
PubMed2001

Locomotor performance of Drosophila melanogaster: interactions among developmental and adult temperatures, age, and geography.

We explored the extent to which a phenotypic trait (walking speed) of Drosophila melanogaster is influenced by population, developmental temperature, adult temperature, and age. Our goals were to estimate the importance of these factors and to test the beneficial acclimation hypothesis. We measured speed of flies from two populations (the Congo and France) that developed at different temperatures (18, 25, and 29 degrees C) and were tested at different temperatures (18, 25, and 29 degrees C) and ages (2, 7, 13 days). Not surprisingly, speed increased strongly with test temperature. Speed was generally greatest for flies reared at an intermediate developmental temperature, contrary to the beneficial acclimation hypothesis, which predicts that speed would be greatest when influenced by interactions involving population. For example, speed was greatest for flies from France that developed at a low temperature, but for flies from the Congo that developed at a high temperature. The impact of developmental temperature declined with age. Surprisingly, speed actually increased with age for flies raised and maintained at a low temperature, but decreased with age for flies raised and maintained at an intermediate or at a high temperature. Thus, walking performance is highly dynamic phenotypically, complicating potential attempts to predict responses to selection on performance.

Acclimatization↗