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Results for “Developmental programming”

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At least 577 records · Page 32Linked to original sources

PubMed1998

Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development.

The cytosolic protein APAF1, human homolog of C. elegans CED-4, participates in the CASPASE 9 (CASP9)-dependent activation of CASP3 in the general apoptotic pathway. We have generated by gene trap a null allele of the murine Apaf1. Homozygous mutants die at embryonic day 16.5. Their phenotype includes severe craniofacial malformations, brain overgrowth, persistence of the interdigital webs, and dramatic alterations of the lens and retina. Homozygous embryonic fibroblasts exhibit reduced response to various apoptotic stimuli. In situ immunodetection shows that the absence of Apaf1 protein prevents the activation of Casp3 in vivo. In agreement with the reported function of CED-4 in C. elegans, this phenotype can be correlated with a defect of apoptosis. Our findings suggest that Apaf1 is essential for Casp3 activation in embryonic brain and is a key regulator of developmental programmed cell death in mammals.

Alleles↗

PubMed1992

Control of constitutively-expressed developmentally-activated rat hepatic cytochrome P450 genes.

Cytochromes P450 (P450) collectively refer to a superfamily of heme-containing enzymes that use O2 and electrons from NADPH to insert a single atom of oxygen into any one of a large number of substrates. Two general classes of P450s exist; a relatively limited number of P450 forms, expressed in specialized tissues that are associated with pathways of steroidogenesis and a large number of forms responsible for metabolism of foreign compounds. Most of the latter P450s are expressed in liver, the primary site for metabolism of drugs, unusual dietary compounds and environmental pollutants. Numerous forms of P450 are expressed in liver of untreated animals and these are regulated quite differently. Both developmentally-programmed and sex-specific expressions have been observed. In this review, I will summarize recent findings on the mechanisms by which two P450 genes are regulated in livers of developing rats. The CYP2E1 gene is transcriptionally activated within a few hours after birth while the CYP2C6 gene is activated just prior to rats reaching puberty. These genes are under control of two transcription factors, HNF-1 alpha and DBP, respectively, that themselves are developmentally controlled.

Albumins↗

PubMed1994

Embryogenic transformation of the suspensor in twin, a polyembryonic mutant of Arabidopsis.

Spontaneous twinning is a widespread but infrequent phenomenon in higher plants. We describe here a mutant of Arabidopsis thaliana, twin, that yields an unusually high frequency of viable twin and occasional triplet seedlings. Supernumerary embryos of twin arise through a novel mechanism: transformation of cells within the suspensor, a differentiated structure established early in embryogenesis. Twin embryos develop in tandem within the seed, connected by intact segments of the suspensor. Transformed suspensor cells appear to duplicate the patterns of cell division and developmental pathways characteristic of zygotic embryogenesis. In addition to polyembryony, mutant embryos exhibit a number of developmental defects, including irregular patterns of cell division and abnormal morphology. The TWIN locus therefore appears to be required for normal development of the embryo proper as well as suppression of embryogenic potential in the suspensor. The development of viable secondary embryos in twin demonstrates that cells of the Arabidopsis suspensor can successfully establish embryonic polarity and complete the full spectrum of developmental programs normally restricted to the embryo proper. In addition, the twin phenotype indicates that disruption of a single genetic locus can result in the conversion of a single terminally differentiated cell type to an embryogenic state.

Arabidopsis↗

PubMed2004

p63 and epithelial appendage development.

Abstract Epithelial appendages share a common developmental program that relies on extensive interactions between epithelia and adjacent mesenchyme. The transcription factor p63 has a critical role in epithelial appendage development in both vertebrates and non-vertebrates. Both mice and zebrafish lacking p63 expression fail to develop epithelial appendages and other structures that develop as a result of epithelial-mesenchymal interactions. Furthermore, dominantly inherited mutations in p63 are the cause of a subset of human ectodermal dysplasias, which are characterized by developmental abnormalities in epithelia and epithelial appendages. While the importance of p63 for epithelial appendage development is evident, the molecular mechanisms by which p63 functions are largely unknown. In this review, we will discuss the current knowledge of the developmental role of p63 and the implications for epithelial appendage development.

Animals↗

PubMed1989

G-protein-linked signal transduction systems control development in Dictyostelium.

G-protein-linked cAMP receptors play an essential role in Dictyostelium development. The cAMP receptors are proposed to have seven transmembrane domains and a cytoplasmic C-terminal region. Overexpression of the receptor in cells, when the endogenous receptor is not present, results in a 10- to 50-fold increase in cAMP-binding sites. Antisense cell lines, which lack cAMP receptors, do not enter the developmental program. Ligand-induced phosphorylation is proposed to occur on serine and threonine residues in the receptor C-terminus. The kinetics of receptor phosphorylation and dephosphorylation correlate closely with the shift of receptor mobility and the adaptation of several cAMP-induced responses. Two alpha-subunits, G-alpha-1 and G-alpha-2, have been cloned and specific antisera developed against each. Both subunits are expressed as multiple RNAs with different developmental time courses. The mutant Frigid A has a functional defect in G-alpha-2 which prevents it from entering development. We propose that G-protein-linked receptor systems will be a major component in the development of many organisms.

Amino Acid Sequence↗

PubMed2005

Ricinosomes and endosperm transfer cell structure in programmed cell death of the nucellus during Ricinus seed development.

The ricinosome (precursor protease vesicle) is an organelle found exclusively in plant cells. Ricinosomes contain a 45-kDa pro-cysteine endopeptidase (CysEP) with a C-terminal KDEL endoplasmic reticulum retention signal. CysEP is a member of a unique group of papain-type cysteine peptidases found specifically in senescing and ricinosome-containing tissues. During seed development in the castor oil plant (Ricinus communis L.), the cells of the nucellus are killed as the major seed storage organ, the cellular endosperm, expands and begins to accumulate reserves. The destruction of the maternal seed tissues is a developmentally programmed cell death. Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling revealed that nuclear DNA fragmentation occurs in the nucellar cells adjacent to the expanding endosperm. These cells exhibit ultrastructural features consistent with programmed cell death, including vesiculation of the cytosol, development of irregularly shaped nuclei, vacuolar collapse, and shrinkage of the cytoplasm. Ricinosomes containing the CysEP were identified in the nucellar cells by light and electron microscopy and immunocytochemistry. Both proCysEP and mature CysEP are present in protein extracts of the nucellar tissues during seed development. Upon collapse of the nucellar cells, the content of the ricinosomes is released into the cytoplasm, where the activated CysEP digests the remaining proteinaceous cellular debris. Digestion products of the nucellar cells are presumed taken up by the outermost cells of the endosperm, which have labyrinthine ingrowths of the outer walls typical of transfer cells.

Apoptosis↗

PubMed1998

Sealing one's fate: control of cell death in neurons.

BCL-2 family members and caspases are essential components of the death machinery in neurons. Identification of Apaf-1 as the mammalian homologue of Caenorhabditis elegans ced-4 provided the final proof of the complete conservation of the C. elegans programmed cell death pathway in mammals. When neurons are deprived of trophic factors, a sequence of events is initiated, which includes a reduction in macromolecule synthesis, elevation of c-Jun and cyclin D1, and activation of BAX. The final episode of this sequence is the activation of caspases, which may mark the death commitment point at which neurons cannot be rescued by addition of trophic factors. In addition, recent evidence suggests that the components in the developmental programmed cell death pathway may play a critical role in neurodegenerative disorders.

Animals↗

PubMed1984

Are limb development and limb regeneration both initiated by an integumentary wounding? A hypothesis.

It is proposed that, whereas an actual wound to a salamander limb may initiate limb regeneration, a local and developmentally programmed integumentary wound may initiate limb development. The electrophysiological changes induced by these lesions of the skin may be a common denominator linking limb regeneration and limb development. Such early electrical events are considered to initiate or guide the early accumulation of cells, and to help to produce the local environment in which a limb will arise. This scheme provides a self-limiting positive-feedback mechanism for the production of a localized area where other developmental mechanisms act in concert with endogenous electrical fields (or in their complete absence), thereby leading to limb differentiation. This hypothesis may not be restricted to limb formation; it may be of more general significance, i.e. in the process of organogenesis in embryos. One might reasonably suggest that, by such a mechanism, any developing placode (for example, auditory or olfactory placodes) might form and localize.

Amphibians↗

PubMed1997

Alternative splicing of the sodium channel SCN8A predicts a truncated two-domain protein in fetal brain and non-neuronal cells.

The voltage-gated sodium channel alpha subunit SCN8A is one of the most abundant sodium channels in neurons from brain and spinal cord. We have identified two alternatively spliced exons, 18N and 18A, that encode transmembrane segments S3 and S4 in domain III. Exon 18N is expressed in fetal brain and non-neuronal tissues. Transcripts with exon 18N have a conserved in-frame stop codon that predicts the synthesis of a truncated, two-domain protein similar to the fetal form of the muscle calcium channel. The proportion of transcripts containing exon 18N is highest in mouse fetal brain between E12.5 and P1.5; at later ages transcripts containing exon 18A predominate. This developmental program is recapitulated in P19 cells during retinoic acid-induced neuronal differentiation. Non-neuronal tissues contain a low level of SCN8A transcripts containing exon 18N. SCN8A thus provides a new model of differentiation specific splicing. Genomic analysis of SCN8A from human, mouse, and fish demonstrated a conserved structure in which exon 18N is located 300-500 bp upstream of exon 18A. Duplication of exon 18 thus preceded the divergence of fish and mammals. The genomic organization, developmental regulation, and coding content of exons 18N and 18A closely resemble the previously described alternate exons 5N and 5A of the neuronal sodium channel genes. Our proposal that the evolutionary origin of exons 18N and 18A was by duplication of exons 5N and 5A is consistent with other evidence that the four-domain cation channels arose by two rounds of duplication from a single-domain ancestral channel.

Alternative Splicing↗

PubMed2000

Genome-wide expression profiling of mid-gestation placenta and embryo using a 15,000 mouse developmental cDNA microarray.

cDNA microarray technology has been increasingly used to monitor global gene expression patterns in various tissues and cell types. However, applications to mammalian development have been hampered by the lack of appropriate cDNA collections, particularly for early developmental stages. To overcome this problem, a PCR-based cDNA library construction method was used to derive 52,374 expressed sequence tags from pre- and peri-implantation embryos, embryonic day (E) 12.5 female gonad/mesonephros, and newborn ovary. From these cDNA collections, a microarray representing 15,264 unique genes (78% novel and 22% known) was assembled. In initial applications, the divergence of placental and embryonic gene expression profiles was assessed. At stage E12.5 of development, based on triplicate experiments, 720 genes (6.5%) displayed statistically significant differences in expression between placenta and embryo. Among 289 more highly expressed in placenta, 61 placenta-specific genes encoded, for example, a novel prolactin-like protein. The number of genes highly expressed (and frequently specific) for placenta has thereby been increased 5-fold over the total previously reported, illustrating the potential of the microarrays for tissue-specific gene discovery and analysis of mammalian developmental programs.

Amino Acid Sequence↗

PubMed2006

Molecular phylogenetics of the Anolis onca series: a case history in retrograde evolution revisited.

Anoles of the Anolis onca series represent a dramatic case of retrograde evolution, exhibiting great reduction (A. annectens) and loss (A. onca) of the subdigital pads considered a key innovation for the evolutionary radiation of anoles in arboreal environments. We present a molecular phylogenetic analysis of these anoles and their closest known relatives (A. auratus, A. lineatus, A. meridionalis, and A. nitens) using new mitochondrial DNA sequence data from the ND2 gene, five tRNA genes (tRNA(Trp), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr)), the origin of light-strand replication, and a portion of the CO1 gene (1,446 aligned base positions, 612 parsimony informative). Our results confirm monophyly of the A. onca series and suggest an evolutionary separation of approximately 10 million years between A. annectens and A. onca. Evolution of subdigital structure in this series illustrates ectopic expression of developmental programs that replace flexible subdigital lamellae of the toepad with rigid, keeled scales resembling dorsal digital scales. Our phylogenetic results indicate that narrowing of the toepad in A. auratus evolved separately from toepad reduction in the A. onca series. Expansion of the subdigital lamellae along the phalanges in A. auratus appears to compensate constriction of lamellae by digital narrowing, maintaining greater climbing capability in this species. Toepad evolution in the lineage ancestral to A. auratus features changes of the same developmental modules as the A. onca series but in the opposite direction. Large molecular distances between geographic populations of A. auratus indicate that its derived toepad structure is at least 9 million years old.

Animals↗

PubMed2004

After-school youth development programs: a developmental-ecological model of current research.

Although there has been a rapid increase in funding and attention to after-school programs, there is little understanding of how after-school programs impact children's developmental trajectories. The heterogeneity of American children makes it very unlikely that all children need after-school programming or that there is but one brand of after-school programming suitable for all youth. We discuss the numerous developmental and contextual factors that may influence which children benefit most from after-school programs as well as the nature of the after-school programs most beneficial to children's needs. The value of utilizing an ecological and developmental perspective to after-school program evaluation are presented, including the need for improved research designs and more detailed analyses of program type and services as well as a more complete determination of which children benefit the most from after-school participation.

Black or African American↗

PubMed1997

HNF-6 is expressed in endoderm derivatives and nervous system of the mouse embryo and participates to the cross-regulatory network of liver-enriched transcription factors.

Hepatocyte nuclear factor-6 (HNF-6) is a liver-enriched transcription factor that contains a single cut domain and a novel type of homeodomain. Here we have studied the developmental expression pattern of HNF-6 in the mouse. In situ hybridization experiments showed that HNF-6 mRNA is detected in the liver at embryonic day (E) 9, at the onset of liver differentiation. HNF-6 mRNA disappeared transiently from the liver between E12.5 and E15. In transfection experiments HNF-6 stimulated the expression of HNF-4 and of HNF-3 beta, two transcription factors known to be involved in liver development and differentiation. HNF-6 was detected in the pancreas from E10.5 onward, where it was restricted to the exocrine cells. HNF-6 was also detected in the developing nervous system. Both the brain and the spinal cord started to express HNF-6 at E9-9.5 in postmitotic neuroblasts. Later on, HNF-6 was restricted to brain nuclei, to the retina, to the ventral horn of the spinal cord, and to dorsal root ganglia. Our observations that HNF-6 contributes to the control of the expression of transcription factors and is expressed at early stages of liver, pancreas, and neuronal differentiation suggest that HNF-6 regulates several developmental programs.

Animals↗

PubMed1998

Development of polyembryonic insects: a major departure from typical insect embryogenesis.

The parasitic wasp Copidosoma floridanum represents the most extreme form of polyembryonic development known, forming up to 2000 embryos from a single egg. To understand the mechanisms of embryonic patterning in polyembryonic wasps and the evolutionary changes that led to this form of development we have analyzed embryonic development at the cellular level using confocal and scanning electron microscopy. C. floridanum embryogenesis can be divided into three phases: (1) early cleavage that leads to formation of a primary morula, (2) a proliferative phase that involves partitioning of embryonic cells into thousands of morulae, and (3) morphogenesis whereby individual embryos develop into larvae. This developmental program represents a major departure from typical insect embryogenesis, and we describe several features of morphogenesis unusual for insects. The early development of polyembryonic wasps, which likely evolved in association with a shift in life history to endoparasitism, shows several analogies with mammalian embryogenesis, including early separation of extraembryonic and embryonic cell lineages, formation of a morula and embryonic compaction. However, the late morphogenesis of polyembryonic wasps proceeds in a fashion conserved in all insects. Collectively, this suggests a lack of developmental constraints in early development, but a strong conservation of the phylotypic stage.

Animals↗

PubMed1998

Extracellular matrix remodeling during morphogenesis.

The role of proteinases in extracellular matrix remodeling during the developmental program of bone, cartilage, muscle, and epithelial differentiation in the mandibular arch during embryogenesis was investigated. ECM changes accompany morphogenesis during development. The most dramatic changes occur during development of bone and cartilage. The expression of matrix metalloproteinases (MMPs) was altered by regulating expression of MMPs by growth factors, by inhibiting MMP activity, and by genetic ablation of MMPs. The data point to critical roles for MMPs in cartilage development and endochondral bone formation. MMPs appear to regulate not only ECM degradation but also programmed cell death, cell migration, and invasion during these morphogenic processes. The data suggest that matrix metalloproteinases play a pivotal role in the morphogenesis of structures derived from epithelium (oral sulcus), somitic mesoderm (tongue), and cranial neural crest (Meckel's cartilage).

Animals↗

PubMed1997

Anti-adhesive signals are mediated via major histocompatibility complex class II molecules in normal and neoplastic human B cells: correlation with B cell differentiation stage.

We show that major histocompatibility complex (MHC) class II molecules on B cells transit signals which regulate adhesion in a negative manner. Engagement of MHC class II molecules with antibodies results in detachment of B cells previously bound to interferon-gamma-activated human umbilical cord venous endothelial cells. This process depends on metabolic energy, active signaling and protein tyrosine kinase activity. The adhesion pathway influenced by this signaling event is neuraminidase sensitive. The anti-adhesive signaling program is activated in B cell lines with a mature phenotype, e.g. normal B cells from spleen and tonsil. In contrast, cell lines with a pre-B cell phenotype and normal B cells from peripheral blood are refractory to MHC class II-mediated regulation of adhesion. These results extend to neoplastic cells from patients with lymphoproliferative diseases representing different stages of B cell maturation. These results suggest that MHC class II-mediated signals regulate B cell adhesion in a developmentally programmed fashion; this might have implications for clinical behavior of B cell malignancies.

Animals↗

PubMed1995

Translational regulation: versatile mechanisms for metabolic and developmental control.

It has become clear that many vital metabolic circuits and early developmental programs are regulated translationally. Until recently, the mechanisms underlying most of these observations were poorly understood. The past year has witnessed several important advances in the understanding of how the translational apparatus is controlled by different regulatory mechanisms.

Animals↗

PubMed1998

Vitellin processing and protein synthesis during cricket embryogenesis.

At the start of insect embryogenesis most of the protein mass of the egg cytoplasm exists as vitellin (Vt) obtained endocytically during vitellogenesis. Of the new embryo polypeptides (EP) appearing in the egg during embryogenesis, many are synthesized de novo, while, in some species, others derive from developmentally programmed partial proteolysis of Vt. Earlier we showed that by the end of vitellogenesis the two native Vts in Acheta domesticus exist in opposing gradients along the longitudinal axis of the egg. Here we hypothesize that this ooplasmic Vt distribution presents a milieu for Vt processing out of which region-specific regulatory molecules could arise. The metabolic origin and stage-specific patterns of seven predominant EPs (EP 1-7) identified by SDS-PAGE were examined and the results correlated with developmental morphology during the 14 days of embryogenesis. Based on antibody reactivity, peptide mapping and in vitro radiolabeling, we determined that EPs 1-3, 6 and 7 are Vt-derived, while EPs 4 and 5 are produced de novo by the embryo. The five Vt-derived EPs appear during the first 24 h of embryogenesis when migrating cleavage nuclei and associated cytoplasm form the cellular blastoderm, and levels of EPs 4 and 5 increase during days 4-6 of embryogenesis when katatrepsis and yolk mass contraction occur. Positive periodic acid-Schiff staining indicated that EPs 1-3 and their Vt-precursor polypeptides are glycoproteins. This work shows that developmental stage-specific Vt processing occurs during A. domesticus embryogenesis and points next to investigation of the functional significance of Vt cleavage products during development.

Animals↗