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Results for “Developmental programming”

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PubMed1992

Developing in a family way. Transforming Growth Factor Type beta and Related Proteins in Development: the Sixth Molecular, Cellular and Developmental Biology/Iowa State University Symposium, Ames, IA, USA September 20-23, 1991.

We are left with the impression that members of the TGF-beta family are critically positioned in a cascade of events regulating complex developmental processes. Roberts described the TGF-betas as providing the cells with cues to their temporal positions in a developmental program, that is, telling the cells "where they were, where they are, and where they're going." The broad diversity of cellular and tissue responses to TGF-betas and the widespread expression of their receptors suggest the TGF-betas may act as a "common currency," enabling diverse cell types to communicate with each other. Other members of the family are more restricted in their expression and the expression of their receptors, and may have a more limited and well-defined developmental role. The complex regulation of the members of the TGF-beta family is consistent with their importance as directors and coordinators of complicated physiological processes such as those occurring in the development of multicellular organisms. Their expression is highly regulated at the transcriptional and post-transcriptional levels, and their localization and activation can be affected by binding proteins and matrix proteins. We still have much to learn about the receptors for this family of growth factors, but the recent cloning of the activin and TGF-beta receptors and the discovery of their enzymatic nature has dramatically opened the way for future studies to resolve the signal transduction pathway(s) used by members of this family.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

T-cell receptor genes in autoimmune mice: T-cell subsets have unexpected T-cell receptor gene programs.

Two unique cell subsets have been identified in the autoimmune-prone MRL/MP lpr/lpr and C3H/HeJ gld/gld murine strains that have the Lyt-2-,L3T4-,Thy-1+, and Lyt-2-,L3T4-,Ia-,Thy-1- phenotypes, respectively. We have now found that these cells express T-cell receptor proteins on their surface. Our observations further indicate that the expression of the Thy-1 antigen does not correlate with the expression of alpha-chain and beta-chain T-cell receptor polypeptides. Interestingly, T-cell receptor gamma-chain RNA expression may be influenced or correlate with Thy-1 molecular expression. These studies indicate unusual relationships of different cell-surface structures that may reflect unexpected developmental programs.

Animals↗

PubMed1998

Developmentally regulated nuclear transport of transcription factors in Drosophila embryos enable the heat shock response.

Hsp70 is a broadly conserved thermotolerance factor, but inhibits growth at normal temperatures and cannot be induced in early embryos. We report that in Drosophila embryos the temporal and spatial patterns of Hsp70 inducibility were unexpectedly complex, with striking differences between the soma and the germline. In both, regulation occurred at the level of transcription. During the refractory period for Hsp70 induction, HSF (heat-shock transcription factor) exhibited specific DNA-binding activity characteristic of activation in extracts of heated embryos. Remarkably, however, HSF was restricted to the cytoplasm in intact embryos even after heat shock. HSF moved from the cytoplasm to the nucleus in the absence of heat precisely when the capacity to induce Hsp70 was acquired (cycle 12 of the germline, cycle 13 in the soma). During oogenesis, Hsp70 inducibility was lost in nurse cells around stage 10, in a posterior-to-anterior gradient and HSF redistributed from nucleus to cytoplasm in the same spatiotemporal pattern. In a highly inbred derivative of the Samarkind strain, HSF moved into embryonic nuclei earlier than in our standard wild-type strain. Correspondingly, Hsp70 was inducible earlier, confirming that nuclear transport of HSF controls the inducibility of Hsp70 in early embryos. We also report for the first time the nuclear import patterns of two general transcription factors, RNA polymerase subunit Ilc and TATA binding protein (TBP). Both enter nuclei in a highly synchronous manner, independently of each other and of HSF. The import of TBP coincides with the first reported appearance of transcripts in the embryo. We suggest that the potentiation of general and heat shock-specific transcription in Drosophila embryos is controlled by the developmentally programmed relocalization of general and heat shock-specific transcription factors. Restricted nuclear entry of HSF represents a newly described mechanism for regulating the heat-shock response.

Animals↗

PubMed2002

A transcriptional profile of multicellular development in Dictyostelium discoideum.

A distinct feature of development in the simple eukaryote Dictyostelium discoideum is an aggregative transition from a unicellular to a multicellular phase. Using genome-wide transcriptional analysis we show that this transition is accompanied by a dramatic change in the expression of more than 25% of the genes in the genome. We also show that the transcription patterns of these genes are not sensitive to the strain or the nutritional history, indicating that Dictyostelium development is a robust physiological process that is accompanied by stereotypical transcriptional events. Analysis of the two differentiated cell types, spores and stalk cells, and their precursors revealed a large number of differentially expressed genes as well as unexpected patterns of gene expression, which shed new light on the timing and possible mechanisms of cell-type divergence. Our findings provide new perspectives on the complexity of the developmental program and the fraction of the genome that is regulated during development.

Animals↗

PubMed2004

Programming of the hypothalamo-pituitary-adrenal axis: serotonergic involvement.

The ability of the early environment to programme the developing hypothalamo-pituitary-adrenal (HPA) axis has been reported in several animal species. There is considerable evidence that a similar process can occur in the human, and that long-term alterations in HPA function are associated with altered susceptibility to disease in later life. The phenotype of HPA function following early manipulation depends on the timing and intensity of the manipulation as well as the gender of the fetus/neonate. There is considerable interplay between the developing HPA and the reproductive axes and emerging evidence indicates that this interaction is modified by early environmental manipulation. Studies are rapidly unravelling the mechanisms that underlie developmental programming of the HPA axis. In this context, the serotonergic system has been identified as a primary system involved in this process. Understanding the mechanisms involved in neuroendocrine programming will facilitate the development of interventions aimed at reversing or ameliorating the impact of an adverse intrauterine environment.

Animals↗

PubMed2000

Alterations in the proteome of the Euprymna scolopes light organ in response to symbiotic Vibrio fischeri.

During the onset of the cooperative association between the Hawaiian sepiolid squid Euprymna scolopes and the marine luminous bacterium Vibrio fischeri, the anatomy and morphology of the host's symbiotic organ undergo dramatic changes that require interaction with the bacteria. This morphogenetic process involves an array of tissues, including those in direct contact with, as well as those remote from, the symbiotic bacteria. The bacteria induce the developmental program soon after colonization of the organ, although complete morphogenesis requires 96 h. In this study, to determine critical time points, we examined the biochemistry underlying bacterium-induced host development using two-dimensional polyacrylamide gel electrophoresis. Specifically, V. fischeri-induced changes in the soluble proteome of the symbiotic organ during the first 96 h of symbiosis were identified by comparing the protein profiles of symbiont-colonized and uncolonized organs. Both symbiosis-related changes and age-related changes were analyzed to determine what proportion of the differences in the proteomes was the result of specific responses to interaction with bacteria. Although no differences were detected over the first 24 h, numerous symbiosis-related changes became apparent at 48 and 96 h and were more abundant than age-related changes. In addition, many age-related protein changes occurred 48 h sooner in symbiotic animals, suggesting that the interaction of squid tissue with V. fischeri cells accelerates certain developmental processes of the symbiotic organ. These data suggest that V. fischeri-induced modifications in host tissues that occur in the first 24 h of the symbiosis are independent of marked alterations in the patterns of abundant proteins but that the full 4-day morphogenetic program requires significant alteration of the host soluble proteome.

Animal Structures↗

PubMed2003

AmphiNk2-tin, an amphioxus homeobox gene expressed in myocardial progenitors: insights into evolution of the vertebrate heart.

We isolated a full-length cDNA clone of amphioxus AmphiNk2-tin, an NK2 gene similar in sequence to vertebrate NK2 cardiac genes, suggesting a potentially similar function to Drosophila tinman and to vertebrate NK2 cardiac genes during heart development. During the neurula stage of amphioxus, AmphiNk2-tin is expressed first within the foregut endoderm, then transiently in muscle precursor cells in the somites, and finally in some mesoderm cells of the visceral peritoneum arranged in an approximately midventral row running beneath the midgut and hindgut. The peritoneal cells that express AmphiNk2-tin are evidently precursors of the myocardium of the heart, which subsequently becomes morphologically detectable ventral to the gut. The amphioxus heart is a rostrocaudally extended tube consisting entirely of myocardial cells (at both the larval and adult stages); there are no chambers, valves, endocardium, epicardium, or other differentiated features of vertebrate hearts. Phylogenetic analysis of the AmphiNk2-tin sequence documents its close relationship to vertebrate NK2 class cardiac genes, and ancillary evidence suggests a relationship with the Drosophila NK2 gene tinman. Apparently, an amphioxus-like heart, and the developmental program directing its development, was the foundation upon which the vertebrate heart evolved by progressive modular innovations at the genetic and morphological levels of organization.

Amino Acid Sequence↗

PubMed2000

Thermal resistance, developmental rate and heat shock proteins in Artemia franciscana, from San Francisco Bay and southern Vietnam.

Cysts (encysted gastrula embryos) of Artemia franciscana collected from salterns in San Francisco Bay, California, USA (SF) were inoculated into much warmer growth ponds in the Mekong Delta region of Vietnam (V) in 1996. V adults arising directly from these cysts during 17 April to 15 May produced their own cysts, which were collected, processed and stored until shipped to the USA for study. Adults grown in the laboratory from SF cysts (those used for the inoculation) were less resistant to high temperature than adults cultured from V cysts. V cysts produced heat-resistant adults, even though cultured under the same laboratory conditions as SF animals, at much lower temperatures than they ever experienced in Vietnam. Differences in thermal performance between SF and V adults were retained in the second generation, cultured from cysts produced in the laboratory by first generation adults, suggesting a genetic basis for the better heat resistance of V adults. We propose that the operation of natural selection in the Vietnam growth ponds produced adults with improved thermal tolerance, and that the basis for this tolerance was incorporated into the developmental program of their cysts. Surprisingly, differences in heat resistance of laboratory reared animals were not reflected in constitutive levels of the hsp70 family which were similar in first generation SF and V adults. A conditioning heat shock (HS, 37 degrees C, 30 min) led to the same level of induced thermotolerance in SF and V first generation adults when evaluated 24 h post-HS. Levels of hsp70 were also up-regulated at that time, but to about the same extent in SF and V adults. Developmental rates of SF cysts used for the inoculation were faster than those of cysts produced in Vietnam when both were incubated at 21+/-1 degrees C, suggesting that V cysts have become adapted to develop at higher temperatures.

Journal Article↗

PubMed2002

Keeping killers on a tight leash: transcriptional and post-translational control of the pro-apoptotic activity of BH3-only proteins.

BH3-only proteins are structurally distant members of the Bcl-2 protein family that trigger apoptosis. Genetic experiments have shown that these proteins are essential initiators of programmed cell death in species as distantly related as mice and C. elegans. BH3-only proteins share with each other and with the remainder of the Bcl-2 family only a nine amino acid BH3 (Bcl-2 Homology) region. Mutational analyses have demonstrated that this domain is required for their ability to bind to Bcl-2-like pro-survival proteins and to initiate apoptosis. So far only one BH3-only protein, EGL-1, has been identified in C. elegans and it is required for all developmentally programmed death of somatic cells in this species. In contrast, mammals have at least 10 BH3-only proteins that differ in their expression pattern and mode of activation. Studies in gene targeted mice have indicated that different BH3-only proteins are required for the initiation of distinct apoptotic stimuli. The pro-apoptotic activities of BH3-only proteins are stringently controlled by a variety of mechanisms. C. elegans egl-1 as well as mammalian hrk/dp5, noxa, puma/bbc3 and bim/bod are regulated by a diverse range of transcription factors. Certain BH3-only proteins, including Bad, Bik/Nbk, Bid, Bim/Bod and Bmf, are restrained by post-translational modifications that cause their sequestration from pro-survival Bcl-2 family members. In this review we describe current knowledge of the functions and transcriptional as well as post-translational control mechanisms of BH3-only proteins.

Animals↗

PubMed1991

Autonomous differentiation of dorsal axial structures from an animal cap cleavage stage blastomere in Xenopus.

Dorsal or ventral blastomeres of the 16- and 32-cell stage animal hemisphere were labeled with a lineage dye and transplanted into the position of a ventral, vegetal midline blastomere. The donor blastomeres normally give rise to substantial amounts of head structures and central nervous system, whereas the blastomere which they replaced normally gives rise to trunk mesoderm and endoderm. The clones derived from the transplanted ventral blastomeres were found in tissues appropriate for their new position, whereas those derived from the transplanted dorsal blastomeres were found in tissues appropriate for their original position. The transplanted dorsal clones usually migrated into the host's primary axis (D1.1, 92%; D1.1.1, 69%; D1.1.2, 100%), and in many cases they also induced and populated a secondary axis (D1.1, 43%; D1.1.1, 67%; D1.1.2, 63%). Bilateral deletion of the dorsal blastomeres resulted in partial deficits of dorsal axial structures in the majority of cases, whereas deletions of ventral midline blastomeres did not. When the dorsal blastomeres were cultured as explants they elongated. Notochord and cement glands frequently differentiated in these explants. These studies show that the progeny of the dorsal, midline, animal blastomeres: (1) follow their normal lineage program to populate dorsal axial structures after the blastomere is transplanted to the opposite pole of the embryo; (2) induce and contribute to a secondary axis from their transplanted position in many embryos; (3) are important for the normal formation of the entire length of the dorsal axis; and (4) autonomously differentiate in the absence of exogenous growth factor signals. These data indicate that by the 16-cell stage, these blastomeres have received instructions regarding their fate, and they are intrinsically capable of carrying out some of their developmental program.

Animals↗

PubMed2001

Genes essential for early events in gonadal development.

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. The basic underlying principle of sexual development is that genetic sex--determined at fertilization by the presence or absence of the Y chromosome--directs the embryonic gonads to differentiate into either testes or ovaries. Thereafter, hormones produced by the testes direct the developmental program that leads to male sexual differentiation. In the absence of testicular hormones, the female pathway of sexual differentiation occurs. Recent studies have defined key roles in gonadal development for two transcription factors: Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After presenting a brief overview of gonadal development and sexual differentiation, this chapter reviews the studies that led to the isolation and characterization of WT1 and SF-1, and then discusses how interactions between these two genes may mediate their key roles in a common developmental pathway.

Animals↗

PubMed1999

Genes essential for early events in gonadal development.

The acquisition of a sexually dimorphic phenotype is a critical event in mammalian development. The basic underlying principle of sexual development is that genetic sex-determined at fertilization by the presence or absence of the Y chromosome--directs the embryonic gonads to differentiate into either testes or ovaries. Thereafter, hormones produced by the testes direct the developmental program that leads to male sexual differentiation. In the absence of testicular hormones, the female pathway of sexual differentiation occurs. Recent studies have defined key roles in gonadal development for two transcription factors: Wilms' tumor suppressor 1 (WT1) and steroidogenic factor 1 (SF-1). After presenting a brief overview of gonadal development and sexual differentiation, this paper reviews the studies that led to the isolation and characterization of WT1 and SF-1, and then discusses how interactions between these two genes may mediate their key roles in a common developmental pathway.

Animals↗

PubMed1996

Physiological roles for parathyroid hormone-related protein: lessons from gene knockout mice.

A null mutation in the PTHrP gene produces profound abnormalities in endochondral bone formation in vivo. The role of PTHrP as a modulator of the chondrocytic proliferation and differentiation program is evident in the alterations that occur in its absence in the temporal and spatial sequence of chondrocyte development and subsequent endochondral bone formation that is necessary for normal bone elongation. These actions of PTHrP are probably responsible for the delay in chondrocyte development seen in Jansen osteochondrodystrophy, a disease caused by ligand-independent activation of the PTH-PTHrP receptor (Schipani et al., 1995). Furthermore, these conclusions have been corroborated by the observation that chondrocyte-specific overexpression of PTHrP causes a profound delay in the developmental program of chondrocyte differentiation and endochondral ossification (Weir et al., 1995). The morphological abnormalities in the knockout mice were limited to the skeletal system, despite the widespread production of PTHrP during fetal development. At this point, one can only speculate about the limited tissue distribution of the abnormalities. It is possible, for example, that other gene products, such as PTH, can compensate for the loss of PTHrP in some tissues. Alternatively, possible abnormalities in proliferation and differentiation may be present but morphologically subtle. A molecular assessment of these possible actions may well reveal more widespread effects of PTHrP.

Animals↗

PubMed1998

Temporal patterns of embryonic gene expression and their dependence on oogenetic factors.

Successful development of a fertilized egg beyond early cleavage divisions requires the de novo initiation and subsequent regulation of embryonic transcription. The egg provides the specialized environment within which the newly formed zygotic nucleus initiates its developmental program and as a result plays an obligatory role in its regulation. Although the precise timing of the onset of embryonic transcription in mammals varies during early cleavage divisions, several common elements exist. In the present essay we review the current literature on the timing and control of embryonic gene expression in mammals, and discuss recent findings from our laboratory on gene expression patterns in bovine embryos and their relation to other species, and zygotic gene activation (ZGA). Lastly, we discuss the putative role of maternally inherited factors in conferring developmental competence to the blastocyst stage, and a method to identify such factors present in oocytes as mRNA.

Animals↗

PubMed1996

Identification of a novel Drosophila opsin reveals specific patterning of the R7 and R8 photoreceptor cells.

The function of the compound eye is dependent upon a developmental program that specifies different cell fates and directs the expression of spectrally distinct opsins in different photoreceptor cells. Rh5 is a novel Drosophila opsin gene that encodes a biologically active visual pigment that is expressed in a subset of R8 photoreceptor cells. Rh5 expression in the R8 cell of an individual ommatidium is strictly coordinated with the expression of Rh3, in the overlying R7 cell. In sevenless mutant files, which lack R7 photoreceptor cells, the expression of the Rh5 protein in R8 cells is disrupted, providing evidence for a specific developmental signal between the R7 and R8 cells that is responsible for the paired expression of opsin genes.

Animals↗

PubMed1999

Pollination, wounding and jasmonate treatments induce the expression of a developmentally regulated pistil dioxygenase at a distance, in the ovary, in the wild potato Solanum chacoense Bitt.

Pollination and fertilization trigger unique developmental programs leading to embryogenesis, ovary maturation and seed set. Pistil tissues are actively involved in pollen tube growth and respond to the presence of the growing pollen tubes by modulating the expression of specific genes. Using subtractive hybridization to isolate genes involved in pollen-pistil interactions and fertilization, we have isolated a pollination- and fertilization-induced dioxygenase which is predominantly expressed in the pistil. In situ hybridization analyses revealed that the SPP2 dioxygenase (Solanum pollinated pistil) from the self-incompatible wild potato Solanum chacoense Bitt. is also developmentally regulated, with mRNA levels gradually regressing from the tip of the style towards the ovary during pistil development. At maturity, the upper limit of SPP2 transcript distribution coincided with the abscission zone of the style and SPP2 dioxygenase expression in ovaries coincided with the fertilization receptivity period of the flower. Pollination, as well as wounding of the style, induced an increase in SPP2 mRNA steady-state levels at a distance, in the ovary. Treatments with stress hormones including methyl jasmonate, jasmonic acid and salicylic acid mimicked the wound response and also induced SPP2 transcripts in the ovary. The SPP2 dioxygenase could be involved in the biosynthesis of deterrent alkaloids in reproductive tissues or in generating chemical signals involved in pollen tube guidance.

Acetates↗

PubMed1997

Differential developmental expression of the rep B and rep D xeroderma pigmentosum related DNA helicase genes from Dictyostelium discoideum.

DNA helicases are essential to many cellular processes including recombination, replication and transcription, and some helicases function in multiple processes. The helicases encoded by the Xeroderma pigmentosum (XP) B and D genes function in both nucleotide excision repair and transcription initiation. Mutations that affect the repair function of these proteins result in XP while mutations affecting transcription result in neurological and developmental abnormalities, although the underlying molecular and cellular basis for these phenotypes is not well understood. To better understand the developmental roles of these genes, we have now identified and characterized the rep B and rep D genes from the cellular slime mold Dictyostelium discoideum . Both genes encode DNA helicases of the SF2 superfamily of helicases. The rep D gene contains no introns and the rep B gene contains only one intron, which makes their genomic structures dramatically different from the corresponding genes in mammals and fish. However the predicted Dictyostelium proteins share high homology with the human XPB and XPD proteins. The single copy of the rep B and D genes map to chromosomes 3 and 1, respectively. The expression of rep B and D (and the previously isolated rep E) genes during multicellular development was examined, and it was determined that each rep gene has a unique pattern of expression, consistent with the idea that they have specific roles in development. The pattern and extent of expression of these genes was not affected by the growth history of the cells, implying that the expression of these genes is tightly regulated by the developmental program. The expression of the rep genes is a very early step in development and may well represent a key event in the initiation of development in this organism.

Amino Acid Sequence↗

PubMed2004

Gibberellins repress photomorphogenesis in darkness.

Plants undergo two different developmental programs depending on whether they are growing in darkness (skotomorphogenesis) or in the presence of light (photomorphogenesis). It has been proposed that the latter is the default pathway followed by many plants after germination and before the seedling emerges from soil. The transition between the two pathways is tightly regulated. The conserved COP1-based complex is central in the light-dependent repression of photomorphogenesis in darkness. Besides this control, hormones such as brassinosteroids (BRs), cytokinins, auxins, or ethylene also have been shown to regulate, to different extents, this developmental switch. In the present work, we show that the hormone gibberellin (GA) widely participates in this regulation. Studies from Arabidopsis show that both chemical and genetic reductions of endogenous GA levels partially derepress photomorphogenesis in darkness. This is based both on morphological phenotypes, such as hypocotyl elongation and hook and cotyledon opening, and on molecular phenotypes, such as misregulation of the light-controlled genes CAB2 and RbcS. Genetic studies indicate that the GA signaling elements GAI and RGA participate in these responses. Our results also suggest that GA regulation of this response partially depends on BRs. This regulation seems to be conserved across species because lowering endogenous GA levels in pea (Pisum sativum) induces full de-etiolation in darkness, which is not reverted by BR application. Our results, therefore, attribute an important role for GAs in the establishment of etiolated growth and in repression of photomorphogenesis.

Arabidopsis↗