TGF beta in murine morphogenetic processes: the early embryo and cardiogenesis

Development ◽  
1990 ◽  
Vol 108 (4) ◽  
pp. 645-656 ◽  
Author(s):  
R.J. Akhurst ◽  
S.A. Lehnert ◽  
A. Faissner ◽  
E. Duffie
Keyword(s):  
Gestational Age ◽  
Translational Control ◽  
Heart Valves ◽  
Cardiac Development ◽  
Biological Effects ◽  
Early Embryo ◽  
Tgf Beta ◽  
Protein Levels ◽  
Developing Heart ◽  
High Level

The tissue distribution of TGF beta-1 RNA was examined within whole mouse embryos from implantation to 10.5 days gestational age and, in the developing heart, up to 8 days postpartum. The earliest high level expression of TGF beta-1 RNA is at 7.0 days postcoitum (p.c.) in the cardiac mesoderm. At 8.0 days gestational age, cardiac TGF beta-1 RNA expression is limited to endocardial cells. By 9.5 days p.c., this expression pattern becomes regionalized to those cells that overlie cardiac cushion tissue. High TGF beta-1 RNA levels continue to persist in endothelial cells of the heart valves until approximately one week postpartum. The TGF beta-1 RNA distribution was compared with the extracellular distributions of polypeptides for TGF beta and J1/tenascin. As previously reported, endothelial expression of TGF beta-1 RNA is correlated with mesenchymal expression of TGF beta polypeptide, suggesting a paracrine mode of action for this growth factor in cardiac development. Minor discrepancies in the distributions of TGF beta-1 RNA and the extracellular form of the TGF beta polypeptide suggest that translational or post-translational control of protein levels occurs and/or the possibility that the antibody used may also recognise other members of the TGF beta polypeptide family. A correlation between endothelial TGF beta-1 expression and distribution of J1/tenascin in the mesenchyme gives further support to the proposition that the biological effects of TGF beta-1 may, in part, be mediated by J1/tenascin.

scholarly journals Computational Modeling of Blood Flow Hemodynamics for Biomechanical Investigation of Cardiac Development and Disease

2021 ◽  
Vol 8 (2) ◽  
pp. 14
Author(s):  
Huseyin Enes Salman ◽  
Huseyin Cagatay Yalcin
Keyword(s):  
Heart Valves ◽  
Developmental Stages ◽  
Cardiac Development ◽  
Morphological Changes ◽  
Heart Defects ◽  
Animal Experiments ◽  
Cfd Modeling ◽  
Cfd Models ◽  
Developing Heart

The heart is the first functional organ in a developing embryo. Cardiac development continues throughout developmental stages while the heart goes through a serious of drastic morphological changes. Previous animal experiments as well as clinical observations showed that disturbed hemodynamics interfere with the development of the heart and leads to the formation of a variety of defects in heart valves, heart chambers, and blood vessels, suggesting that hemodynamics is a governing factor for cardiogenesis, and disturbed hemodynamics is an important source of congenital heart defects. Therefore, there is an interest to image and quantify the flowing blood through a developing heart. Flow measurement in embryonic fetal heart can be performed using advanced techniques such as magnetic resonance imaging (MRI) or echocardiography. Computational fluid dynamics (CFD) modeling is another approach especially useful when the other imaging modalities are not available and in-depth flow assessment is needed. The approach is based on numerically solving relevant physical equations to approximate the flow hemodynamics and tissue behavior. This approach is becoming widely adapted to simulate cardiac flows during the embryonic development. While there are few studies for human fetal cardiac flows, many groups used zebrafish and chicken embryos as useful models for elucidating normal and diseased cardiogenesis. In this paper, we explain the major steps to generate CFD models for simulating cardiac hemodynamics in vivo and summarize the latest findings on chicken and zebrafish embryos as well as human fetal hearts.

scholarly journals Aneuploid abortion correlates positively with MAD1 overexpression and miR-125b down-regulation

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Juan Zhao ◽  
Hui Li ◽  
Guangxin Chen ◽  
Lijun Du ◽  
Peiyan Xu ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Spindle Assembly Checkpoint ◽  
Mitotic Checkpoint ◽  
Early Embryo ◽  
Vital Role ◽  
Control Group ◽  
Embryo Abortion ◽  
Protein Levels ◽  
Mitotic Checkpoint Complex

Abstract Background Aneuploidy is the most frequent cause of early-embryo abortion. Any defect in chromosome segregation would fail to satisfy the spindle assembly checkpoint (SAC) during mitosis, halting metaphase and causing aneuploidy. The mitotic checkpoint complex (MCC), comprising MAD1, MAD2, Cdc20, BUBR1 and BUB3, plays a vital role in SAC activation. Studies have confirmed that overexpression of MAD2 and BUBR1 can facilitate correct chromosome segregation and embryo stability. Research also proves that miR-125b negatively regulates MAD1 expression by binding to its 3′UTR. However, miR-125b, Mad1 and Bub3 gene expression in aneuploid embryos of spontaneous abortion has not been reported to date. Methods In this study, embryonic villi from miscarried pregnancies were collected and divided into two groups (aneuploidy and euploidy) based on High-throughput ligation-dependent probe amplification (HLPA) and Fluorescence in situ hybridization (FISH) analyses. RNA levels of miR-125b, MAD1 and BUB3 were detected by Quantitative real-time PCR (qRT-PCR); protein levels of MAD1 and BUB3 were analysed by Western blotting. Results statistical analysis (p < 0.05) showed that miR-125b and BUB3 were significantly down-regulated in the aneuploidy group compared to the control group and that MAD1 was significantly up-regulated. Additionally, the MAD1 protein level was significantly higher in aneuploidy abortion villus, but BUB3 protein was only mildly increased. Correlation analysis revealed that expression of MAD1 correlated negatively with miR-125b. Conclusion These results suggest that aneuploid abortion correlates positively with MAD1 overexpression, which might be caused by insufficient levels of miR-125b. Taken together, our findings first confirmed the negative regulatory mode between MAD1 and miR-125b, providing a basis for further mechanism researches in aneuploid abortion.

Fertility in Cheviot ewes. 2. The effect of level of pre-mating nutrition on ovulation rate and early embryo mortality in North and South Country Cheviot ewes in moderately-good condition at mating

1979 ◽  
Vol 29 (1) ◽  
pp. 17-23 ◽  
Author(s):  
R. G. Gunn ◽  
J. M. Doney ◽  
W. F. Smith
Keyword(s):  
Food Intake ◽  
Good Condition ◽  
Early Embryo ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Restricted Feeding ◽  
Embryo Mortality ◽  
The North ◽  
Breed Difference ◽  
High Level

ABSTRACTIn two experiments over 2 years, 57 North Country Cheviot and 82 South Country Cheviot hill ewes were differentially group-fed indoors over a 2-month period to achieve either good or moderate body con- dition. Over 5 weeks prior to mating, ewes in good condition were brought down in condition by restricted feeding and ewes in mod- erate condition were raised in condition by a high level of feeding. The ewes were thus in moderately-good condition at mating. After mating, ewes were maintained in this condition until killed either on return to service or at 29 ± 8 days for counts of corpora lutea and viable embryos.Ovulation rate in each breed was positively related to the level of pre-mating food intake at the condition level studied. Embryo mortality, as ova loss, was not influenced overall by the level of pre-mating food intake but loss of multiple-shed ova was greater than that of single-shed ova in ewes which had been on restricted feeding before mating. Although a greater proportion of ewes in the North Country Cheviot breed were not pregnant at slaughter, this could not be identified as a breed difference since the breeds were studied in different years.

scholarly journals The effect of long-term treatment with steroid hormones or tamoxifen on oestrogen receptors (alpha and beta) in the endometrium of ovariectomized cynomolgus macaques

2002 ◽  
Vol 175 (3) ◽  
pp. 673-681 ◽  
Author(s):  
H Wang ◽  
E Isaksson ◽  
B Von Schoultz ◽  
JM Cline ◽  
L Sahlin
Keyword(s):  
Hormone Treatment ◽  
Term Treatment ◽  
Response To Treatment ◽  
Oestrogen Receptors ◽  
Minor Variation ◽  
Protein Levels ◽  
Long Term Treatment ◽  
High Level ◽  
Er Alpha

The effects of oestrogen are mediated by two specific intracellular receptors, oestrogen receptors (ER) alpha and beta, which function as ligand-activated transcriptional regulators. Ovariectomized macaques (Macaca fascicularis) were used to study the regulation of ERalpha and ERbeta in the endometrium by immunohistochemistry and in situ hybridization after long-term hormone treatment. Animals were treated continuously for 35 Months with either conjugated equine oestrogen (CEE), medroxyprogesterone acetate (MPA), combined CEE/MPA, or tamoxifen (TAM). Treatment with CEE/MPA down-regulated ERalpha in the superficial glands. In the superficial stroma the ERalpha level was lower in the CEE/MPA group than in the CEE and MPA groups. ERbeta immunostaining was faint with minor variation in response to treatment, but increased in the superficial stroma after MPA treatment. The ratio of ERbeta/ERalpha increased in superficial stroma and gland after CEE/MPA treatment, and also in stroma after MPA and TAM. Cystic endometrial hyperplasia was observed in TAM-treated animals, in combination with a high level of ERalpha protein expression. The present data show that long-term hormone treatment affects the ERalpha and ERbeta protein levels in the endometrium. The balance between ERalpha and ERbeta seems to be important for the proliferative response to oestrogen.

Simultaneous Determination of α-Fetoprotein and Immunoglobulin Levels From a Microhematocrit Capillary Tube

PEDIATRICS ◽  
1978 ◽  
Vol 61 (2) ◽  
pp. 301-303
Author(s):  
Alfried Kohlschütter
Keyword(s):  
Simultaneous Determination ◽  
Preterm Infants ◽  
Gestational Age ◽  
Capillary Tube ◽  
Long Island ◽  
Internal Diameter ◽  
Protein Levels ◽  
Immunoglobulin Levels ◽  
Blood Volumes

The α-fetoprotein (AFP) concentration in serum is an indicator of gestational age in preterm infants.1 IgM and IgA concentrations are helpful in the diagnosis of perinatal infections.2,3 Determination of all three protein levels can conveniently be made from one single microhematocrit capillary tube. The small blood volumes involved and the simplicity of the procedure make it a tool for routine use in newborn nurseries. The technique described can also be used for the determination of many other compounds. MATERIALS Heparinized microhematocrit capillary tubes (Propper Manufacturing Co., Inc., Long Island, N. Y.) are 75 mm long and have an internal diameter of 1.1 to 1.2 mm.

A genetic pathway for regulation of tra-2 translation

Development ◽  
1997 ◽  
Vol 124 (3) ◽  
pp. 749-758 ◽  
Author(s):  
E.B. Goodwin ◽  
K. Hofstra ◽  
C.A. Hurney ◽  
S. Mango ◽  
J. Kimble
Keyword(s):  
Translational Control ◽  
Direct Repeat ◽  
Postembryonic Development ◽  
Early Embryo ◽  
Translational Repression ◽  
Female Development ◽  
Normal Pattern ◽  
Repeat Elements ◽  
Translation Repression ◽  
Translational Level

In Caenorhabditis elegans, the tra-2 sex-determining gene is regulated at the translational level by two 28 nt direct repeat elements (DREs) located in its 3′ untranslated region (3′UTR). DRF is a factor that binds the DREs and may be a trans-acting translational regulator of tra-2. Here we identify two genes that are required for the normal pattern of translational control. A newly identified gene, called laf-1, is required for translational repression by the tra-2 3′UTR. In addition, the sex-determining gene, tra-3, appears to promote female development by freeing tra-2 from laf-1 repression. Finally, we show that DRF activity correlates with translational repression of tra-2 during development and that tra-3 regulates DRF activity. We suggest that tra-3 may promote female development by releasing tra-2 from translation repression by laf-1 and that translational control is important for proper sex determination--both in the early embryo and during postembryonic development.

Role for mRNA localization in translational activation but not spatial restriction of nanos RNA

Development ◽  
1999 ◽  
Vol 126 (4) ◽  
pp. 659-669 ◽  
Author(s):  
S.E. Bergsten ◽  
E.R. Gavis
Keyword(s):  
Translational Control ◽  
Rna Localization ◽  
Early Embryo ◽  
Posterior Pole ◽  
Translational Repression ◽  
Control Element ◽  
Regulatory Sequences ◽  
Cis Acting ◽  
Body Patterning ◽  
Localization Signal

Patterning of the anterior-posterior body axis during Drosophila development depends on the restriction of Nanos protein to the posterior of the early embryo. Synthesis of Nanos occurs only when maternally provided nanos RNA is localized to the posterior pole by a large, cis-acting signal in the nanos 3′ untranslated region (3′UTR); translation of unlocalized nanos RNA is repressed by a 90 nucleotide Translational Control Element (TCE), also in the 3′UTR. We now show quantitatively that the majority of nanos RNA in the embryo is not localized to the posterior pole but is distributed throughout the cytoplasm, indicating that translational repression is the primary mechanism for restricting production of Nanos protein to the posterior. Through an analysis of transgenes bearing multiple copies of nanos 3′UTR regulatory sequences, we provide evidence that localization of nanos RNA by components of the posteriorly localized germ plasm activates its translation by preventing interaction of nanos RNA with translational repressors. This mutually exclusive relationship between translational repression and RNA localization is mediated by a 180 nucleotide region of the nanos localization signal, containing the TCE. These studies suggest that the ability of RNA localization to direct wild-type body patterning also requires recognition of multiple, unique elements within the nanos localization signal by novel factors. Finally, we propose that differences in the efficiencies with which different RNAs are localized result from the use of temporally distinct localization pathways during oogenesis.

scholarly journals Mammalian E4 Is Required for Cardiac Development and Maintenance of the Nervous System

2005 ◽  
Vol 25 (24) ◽  
pp. 10953-10964 ◽  
Author(s):  
Chie Kaneko-Oshikawa ◽  
Tadashi Nakagawa ◽  
Mitsunori Yamada ◽  
Hiroo Yoshikawa ◽  
Masaki Matsumoto ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cardiac Muscle ◽  
Cardiac Development ◽  
Physiological Function ◽  
Embryonic Fibroblasts ◽  
Adult Mice ◽  
Developing Heart ◽  
Ubiquitin Conjugation ◽  
Spinocerebellar Neurons

ABSTRACT Ubiquitin conjugation typically requires three classes of enzyme: E1, E2, and E3. A fourth type of enzyme (E4), however, was recently shown to be required for the degradation of certain types of substrate in yeast. We previously identified UFD2a (also known as E4B) as an E4 in mammals. UFD2a is exclusively expressed in cardiac muscle during mouse embryonic development, but it is abundant in neurons of adult mice and is implicated in the pathogenesis of neurodegenerative disease. The precise physiological function of this enzyme has remained largely unknown, however. Here, we show that mice lacking UFD2a die in utero, manifesting marked apoptosis in the developing heart. Polyubiquitylation activity for an E4 substrate was greatly reduced in Ufd2a −/− mouse embryonic fibroblasts. Furthermore, Ufd2a +/− mice displayed axonal dystrophy in the nucleus gracilis, as well as degeneration of Purkinje cells accompanied by endoplasmic reticulum stress. These animals also developed a neurological disorder. UFD2a thus appears to be essential for the development of cardiac muscle, as well as for the protection of spinocerebellar neurons from degeneration induced by endoplasmic reticulum stress.

scholarly journals Tunable protein synthesis by transcript isoforms in human cells

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Stephen N Floor ◽  
Jennifer A Doudna
Keyword(s):  
Translational Control ◽  
Protein Production ◽  
Dynamic Range ◽  
Human Cells ◽  
Untranslated Regions ◽  
Specific Expression ◽  
Transcript Isoforms ◽  
Protein Levels ◽  
Eukaryotic Genes ◽  
Control Protein

Eukaryotic genes generate multiple RNA transcript isoforms though alternative transcription, splicing, and polyadenylation. However, the relationship between human transcript diversity and protein production is complex as each isoform can be translated differently. We fractionated a polysome profile and reconstructed transcript isoforms from each fraction, which we term Transcript Isoforms in Polysomes sequencing (TrIP-seq). Analysis of these data revealed regulatory features that control ribosome occupancy and translational output of each transcript isoform. We extracted a panel of 5′ and 3′ untranslated regions that control protein production from an unrelated gene in cells over a 100-fold range. Select 5′ untranslated regions exert robust translational control between cell lines, while 3′ untranslated regions can confer cell type-specific expression. These results expose the large dynamic range of transcript-isoform-specific translational control, identify isoform-specific sequences that control protein output in human cells, and demonstrate that transcript isoform diversity must be considered when relating RNA and protein levels.

scholarly journals Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

2013 ◽  
Vol 45 (4) ◽  
pp. 127-137 ◽  
Author(s):  
Lingchen Fu ◽  
Michael S. Kilberg
Keyword(s):  
Amino Acid ◽  
Transcriptional Activation ◽  
Translational Control ◽  
Mammalian Cells ◽  
Transcriptional Control ◽  
Present Report ◽  
Binding Activity ◽  
Maximal Response ◽  
Protein Levels ◽  
Amino Acid Response

Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.

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