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Results for “Developmental programming”

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PubMed1998

Syntagms in development and evolution.

The genetic analysis of segmentation, neurogenesis, appendage formation and other developmental processes has revealed that the development of Drosophila can be broken down into discrete elementary operations. Thus development can be viewed as a stepwise process where each step is driven by a small group of genes working interactively. García-Bellido proposed that each of these groups be called a "syntagm". In this review, we will describe a series of developmental syntagms, and explore the consequences of this discontinuous organization of the developmental program on evolution.

Animals↗

PubMed2004

Are there biological programming effects for psychological development? Findings from a study of Romanian adoptees.

Associations between experiences and outcomes could be due to (a) continuation of adversity or (b) organismic changes, including experience-expectant and experience-adaptive developmental programming. The adoption into British families of children who had been reared in profoundly depriving institutions in Romania presented an opportunity to test mechanisms. Romanian children reared from infancy in very depriving institutions for periods up to 42 months were compared with 52 nondeprived UK-born children placed into adoptive families before the age of 6 months. The results at 6 years of age showed substantial normal cognitive and social functioning after the provision of family rearing but also major persistent deficits in a substantial minority. The pattern of findings suggests some form of early biological programming or neural damage stemming from institutional deprivation, but the heterogeneity in outcome indicates that the effects are not deterministic.

Adoption↗

PubMed2006

A noncoding RNA is a potential marker of cell fate during mammary gland development.

PINC is a large, alternatively spliced, developmentally regulated, noncoding RNA expressed in the regressed terminal ductal lobular unit-like structures of the parous mammary gland. Previous studies have shown that this population of cells possesses not only progenitor-like qualities (the ability to proliferate and repopulate a mammary gland) and the ability to survive developmentally programmed cell death but also the inhibition of carcinogen-induced proliferation. Here we report that PINC expression is temporally and spatially regulated in response to developmental stimuli in vivo and that PINC RNA is localized to distinct foci in either the nucleus or the cytoplasm in a cell-cycle-specific manner. Loss-of-function experiments suggest that PINC performs dual roles in cell survival and regulation of cell-cycle progression, suggesting that PINC may contribute to the developmentally mediated changes previously observed in the terminal ductal lobular unit-like structures of the parous gland. This is one of the first reports describing the functional properties of a large, developmentally regulated, mammalian, noncoding RNA.

Alternative Splicing↗

PubMed1988

Developmental changes in K+-selective channel activity during differentiation of the Purkinje neuron in culture.

The cerebellar Purkinje neuron cultured from 20 d rat embryos is electrically inexcitable when immature, and acquires excitable membrane properties according to a programmed developmental sequence, thus providing a useful model for investigating mechanisms of CNS neuronal development. Using conventional patch-clamp techniques, we have characterized the the predominant classes of active K+-selective channels at a range of ages encompassing the entire developmental process from 5 to 29 d in vitro (DIV), and have shown pharmacologically that these channels are important contributors to the patterns of spontaneous activity generated by the Purkinje neurons. The 4 predominant classes of K+ channels that are active during steady-state depolarizing voltage commands are identified by unit conductances as the 27, 44, 70, and 100 pS channels, and show differences in several properties, including voltage dependence, sensitivity to tetraethylammonium chloride (TEA), mean open time, and time of appearance during development. Intracellular current-clamp recordings show that physiological maturation of the Purkinje neuron entails increases in the firing rate, the diversity of spike events that comprise spontaneous activity, and the sensitivity of spontaneous activity to disruption by the K+ channel blocker TEA. This increase in sensitivity to TEA correlates with the new expression of activity of the larger-conductance TEA-sensitive classes of K+ channel (70 and 100 pS types). These data show that developmental regulation of the activity of K+-selective channels contributes significantly to the ionic mechanisms that underlie the developmental transitions in spontaneous activity patterns in the Purkinje neuron.

Animals↗

PubMed2001

Macro-evolution of the hairy enhancer in Drosophila species.

It has been suggested that many of the changes in the developmental program might be in the cis-acting promoters and enhancer regions. Here I study the macro-evolutionary changes of an enhancer region for the early developmental gene hairy in Drosophila melanogaster, D. simulans, D. pseudoobscura, D. willistoni, D. nebulosa, D. hydei, and D. virilis. The enhancer region is characterized by small, highly conserved blocks interspersed among highly variable regions. Nevertheless, species phylogenies constructed by the enhancer sequences agree with the widely accepted phylogeny of these species. The evolution of the variable regions is consistent with a molecular clock, while the evolution of the conserved blocks is significantly different from a clock. In particular, the D. pseudoobscura lineage shows the highest degree of species-specific change consistent with changes in expression timing reported in an earlier study. It has been suggested that the variation in sequence length between highly conserved blocks may play a role in the coordination of regulatory processes, such as protein-protein interactions; thus, stabilizing selection has been suggested to act on the length variations. Here I develop a test for stabilizing selection on length variation and show that the hairy enhancer does not show statistically significant evidence for stabilizing selection. J. Exp. Zool. (Mol. Dev. Evol.) 291:175-185, 2001.

Amino Acid Sequence↗

PubMed1990

Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice.

To understand the function of murine homeobox genes, a genetic analysis is mandatory. We generated gain-of-function mutants by introducing genomic sequences of the Hox-1.1 gene under the control of a chicken beta-actin promoter into mice. Our previous data had shown that these transgenic mice are nonviable after birth and are born with craniofacial abnormalities. In a subsequent detailed analysis of severely affected animals, malformations of the basioccipital bone, the atlas, and the axis were observed. Manifestation of an additional vertebra, a proatlas, occurred at the craniocervical transition. The dominant interference of the Hox-1.1 transgene with developmental programs seems to occur around day 9 of gestation, the time of neural crest migration and somite differentiation. We discuss the resulting phenotype with respect to a developmental control function of Hox-1.1.

Animals↗

PubMed1991

Steroid hormones as mediators of neural plasticity.

Steroid and thyroid hormone receptors are expressed in the developing brain and persist throughout adult life. They mediate a variety of effects on the brain, ranging from developmental effects of thyroid hormone and the process of sexual differentiation to the cyclic changes during reproductive cycles in adult female animals. This review summarizes data from the author's laboratory on three topics: (1) actions of extradiol and progesterone on the ventromedial nucleus of the hypothalamus in adult female and male rats, showing both the cyclicity and the consequences of brain sexual differentiation; (2) actions of estradiol on the cholinergic neurons of the basal forebrain of the female and male rat, reflecting the plasticity of the adult cholinergic system as well as sex differences which are developmentally programmed; and (3) diverse actions of estrogens, thyroid hormone and glucocorticoids on the morphology of hippocampal neurons. The review concludes by discussing the interactions between "organizational" (i.e. developmental) effects and the "activational" effects of steroids on the mature nervous system in relation to the environmental control of brain gene expression.

Animals↗

PubMed1995

dad-1, an endogenous programmed cell death suppressor in Caenorhabditis elegans and vertebrates.

Programmed cell death (apoptosis) is a normally occurring process used to eliminate unnecessary or potentially harmful cells in multicellular organisms. Recent studies demonstrate that the molecular control of this process is conserved phylogenetically in animals. The dad-1 gene, which encodes a novel 113 amino acid protein, was originally identified in a mutant hamster cell line (tsBN7) that undergoes apoptosis at restrictive temperature. We have identified a dad-1 homologue in Caenorhabditis elegans (Ce-dad-1) whose predicted product is > 60% identical to vertebrate DAD-1. A search of the sequence databases indicated that DAD-1-like proteins are also expressed in two plant species. Expression of either human dad-1 or Ce-dad-1 under control of a C.elegans heat-shock-inducible promoter resulted in a reduction in the number of programmed cell death corpses visible in C.elegans embryos. Extra surviving cells were present in these animals, indicating that both the human and C.elegans dad-1 genes can suppress developmentally programmed cell death. Ce-dad-1 was found to rescue mutant tsBN7 hamster cells from apoptotic death as efficiently as the vertebrate genes. These results suggest that dad-1, which is necessary for cell survival in a mammalian cell line, is sufficient to suppress some programmed cell death in C.elegans.

Amino Acid Sequence↗

PubMed2006

Activation of oocytes after nuclear transfer.

After nuclear transfer, the recipient oocyte must be stimulated to initiate development. This stimulation is achieved by inducing changes in the oocyte cytoplasm that normally are triggered by the sperm during fertilization. In most cases, such changes include a transient increase in the intracellular-free calcium concentration induced by an electrical pulse or alternatively, by chemical agents. Many times, particularly in aged oocytes, this calcium signal is sufficient to stimulate the oocyte developmental program. Other activation protocols were designed to target pathways downstream of the initial calcium signal to affect the activity of regulatory proteins that play central roles in maintaining developmental arrest. This is achieved by the application of protein kinase or protein synthesis inhibitors; combined with a calcium stimulus such inhibitors are widely used for oocyte activation after nuclear transfer and are able to support embryonic development to term.

Animals↗

PubMed1984

The developmental capacity of mouse oocytes that matured spontaneously in vitro is normal.

The aim of this project was to compare the developmental capacities of mouse oocytes matured in vivo and in vitro. The frequencies of fertilization, preimplantation development, and birth of live offspring after transfer of morulae to uteri of pseudopregnant foster mothers were compared after germinal vesicle stage oocytes underwent spontaneous maturation in vitro, and after gonadotropin-induced maturation in vivo and ovulation. Both groups of matured ova were fertilized in vitro, and preimplantation development was carried out in vitro. Equivalent developmental capacities were observed for all comparisons between the two groups of oocytes. The acquisition of normal developmental capacity depended on the presence of serum in the oocyte maturation medium. The expansion (mucification) of the cumulus oophorus was not required for fertilization or normal development. The frequency of fertilization was lower in oocytes that matured while denuded of cumulus cells. However, when fertilization did occur in these oocytes, a normal percentage developed to live offspring. It is concluded that a normal developmental program occurs during spontaneous maturation of mouse oocytes, and that the presence of cumulus cells during spontaneous maturation may affect the oocyte's fertilizability rather than its subsequent developmental capacity.

Animals↗

PubMed1988

Alterations of cell-surface carbohydrates during differentiation and development.

Expression of many cell-surface carbohydrates is controlled temporally and spatially by developmental programs. This subject is reviewed from 5 viewpoints: structural changes revealed by chemical analysis, cell-surface markers useful for cell identification and separation, core proteins carrying the developmentally regulated carbohydrate chain, glycosyltransferases responsible for the change and the biological meaning of the phenomenon. The differentiation systems covered are mainly early mammalian embryogenesis and the differentiation of blood and nerve cells.

Animals↗

PubMed2006

Pristionchus.org: a genome-centric database of the nematode satellite species Pristionchus pacificus.

Comparative studies have been of invaluable importance to the understanding of evolutionary biology. The evolution of developmental programs can be studied in nematodes at a single cell resolution given their fixed cell lineage. We have established Pristionchus pacificus as a major satellite organism for evolutionary developmental biology relative to Caenorhabditis elegans, the model nematode. Online genomic information to support studies in this satellite system can be accessed at http://www.pristionchus.org. Our web resource offers diverse content covering genome browsing, genetic and physical maps, similarity searches, a community platform and assembly details. Content will be continuously improved as we annotate the P.pacificus genome, and will be an indispensable resource for P.pacificus genomics.

Animals↗

PubMed1982

Hormonal effects on partitioning of nutrients for tissue growth: role of growth hormone and prolactin.

The growth process exemplifies changes in the priorities of different tissues for available nutrients according to a developmental program. We propose that a higher order of endocrine regulation over and above that provided by homeostatic mechanisms directs the flow of nutrients to support the physiological or developmental process of highest prevailing priority. The term homeorhesis is applied to this regulatory phenomenon and is distinguished from the more familiar concept of homeostasis. The documented actions of growth hormone and prolactin as somatotrophic agents are discussed and their candidacy as likely homeorhetic vectors is proposed. Certain shortcomings in the quality of available hormone preparations and inconsistencies between potencies in various tests performed in vitro and in vivo are noted. We question the appropriateness of the use of experimental routines suited to exploring acute metabolic phenomena in acquiring a deeper understanding of the long-term process of growth. Despite the varied nature of supportive data, growth hormone, prolactin, and the closely related placental somatomammotropin exhibit the desired properties of homeorhetic hormones--they direct the flow of nutrients to the process of highest priority, partly by coordinating nutrient utilization by competing tissues.

Adipose Tissue↗

PubMed1996

Programmed DNA rearrangement from an intron during nuclear development in Tetrahymena thermophila: molecular analysis and identification of potential cis-acting sequences.

During macronuclear development in the ciliate Tetrahymena thermophila, extensive rearrangement events occur as DNA deletions. We have studied a developmentally programmed deletion called mse2.9 that occurs within an intron in a gene in both genomic DNA and in an rDNA vector introduced into the cell by transformation. Extensive microheterogeneity at the deletion junctions has been found in caryonidal strains and in the rDNA in transformed cells. A transformation assay has been used to identify sequences required for proper processing of mse2.9. Models to explain deletion site selection as well as microheterogeneity at junction sites are presented.

Animals↗

PubMed1996

From seed germination to flowering, light controls plant development via the pigment phytochrome.

Plant growth and development are regulated by interactions between the environment and endogenous developmental programs. Of the various environmental factors controlling plant development, light plays an especially important role, in photosynthesis, in seasonal and diurnal time sensing, and as a cue for altering developmental pattern. Recently, several laboratories have devised a variety of genetic screens using Arabidopsis thaliana to dissect the signal transduction pathways of the various photoreceptor systems. Genetic analysis demonstrates that light responses are not simply endpoints of linear signal transduction pathways but are the result of the integration of information from a variety of photoreceptors through a complex network of interacting signaling components. These signaling components include the red/far-red light receptors, phytochromes, at least one blue light receptor, and negative regulatory genes (DET, COP, and FUS) that act downstream from the photoreceptors in the nucleus. In addition, a steroid hormone, brassinolide, also plays a role in light-regulated development and gene expression in Arabidopsis. These molecular and genetic data are allowing us to construct models of the mechanisms by which light controls development and gene expression in Arabidopsis. In the future, this knowledge can be used as a framework for understanding how all land plants respond to changes in their environment.

Germination↗

PubMed2005

An organized medullary epithelial structure in the normal thymus expresses molecules of respiratory epithelium and resembles the epithelial thymic rudiment of nude mice.

The expression of tissue-specific Ags (TSA) within the thymic environment has emerged as an important contribution to the establishment of self-tolerance. The mechanistic basis for this property is poorly understood. One model has proposed stochastic derepression of gene expression by mature medullary epithelial cells, whereas another model has suggested that this property of thymic epithelial cells reflects transcriptional activity during their differentiation. Most of the analyses of thymic TSA expression have been done with populations of dissociated thymic epithelial cells; therefore, there is little information regarding the spatial pattern of TSA expression within the thymus. We have evaluated a subset of thymic epithelial cells in the murine thymus that display several unique features. First, within the normal thymus, they form cysts that express several TSA of respiratory epithelium and exhibit some morphological features consistent with respiratory epithelium. These cells also display a phenotypic profile that has been proposed for immature thymic epithelium. The cystic epithelia in the normal thymus and in the nude thymic rudiment are phenotypically very similar, suggesting that they may have a similar developmental program. The coordinated expression of respiratory TSA by an organized subset of thymic epithelial cells and the phenotypic resemblance of these cells to progenitor cells seem consistent with a developmental basis for TSA expression by thymic epithelial cells. Finally, epitopes that define thymic epithelial heterogeneity are reciprocally expressed by respiratory epithelium, which raises interesting questions regarding the developmental relationship of different endodermal derivatives.

Animals↗

PubMed2006

Coupling cell cycle exit, neuronal differentiation and migration in cortical neurogenesis.

The generation of new neurons in the cerebral cortex requires that progenitor cells leave the cell cycle and activate specific programs of differentiation and migration. Genetic studies have identified some of the molecules controlling these cellular events, but how the different aspects of neurogenesis are integrated into a coherent developmental program remains unclear. One possible mechanism implicates multifunctional proteins that regulate, both cell cycle exit and cell differentiation.(1) A prime example is the cyclin-dependent kinase inhibitor p27(Kip1), which has recently been shown to function beyond cell cycle regulation and promote both neuronal differentiation and migration of newborn cortical neurons, through distinct and separable mechanisms. p27(Kip1) is therefore part of a machinery that couples the multiple events of neurogenesis in the cerebral cortex.

Animals↗

PubMed1990

Complex and diversified regulatory programs control the expression of vertebrate collagen genes.

The collagens represent a family of structurally related but genetically distinct proteins whose function is essential to maintaining the integrity of vertebrate organs. In addition to their supportive roles, collagens influence a variety of developmental programs and physiological processes. Transcription of collagen genes is controlled by a series of complex interactions between cis-acting regulatory elements and trans-acting nuclear factors that have positive or negative effects on gene expression. Collagen synthesis relies on the timely utilization of diversified regulatory programs that employ tissue and cell-type specific promoters and enhancers. Some of these programs lead to the production of structurally variant chains in different tissues, while others shut down synthesis of a specific collagen type during cell differentiation. Still others control collagen expression in distinct cell lineages. The number, complexity, and variety of the mechanisms leading to the diversified expression of the collagen genes illustrate the unique contribution of this family of proteins to multicellular organogenesis.

Animals↗