A Drosophila growth factor homolog, decapentaplegic, regulates homeotic gene expression within and across germ layers during midgut morphogenesis

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1041-1050 ◽  
Author(s):  
G.E. Panganiban ◽  
R. Reuter ◽  
M.P. Scott ◽  
F.M. Hoffmann
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Homeotic Gene ◽  
Homeotic Genes ◽  
Germ Layers ◽  
Visceral Mesoderm ◽  
Endodermal Cells ◽  
Homeotic Gene Expression

The decapentaplegic (dpp) gene product, a member of the transforming growth factor-beta family, is required in Drosophila embryos for normal gastrulation and the establishment of dorsal-ventral polarity in the embryo. dpp is also expressed at specific positions in the visceral mesoderm along the developing midgut. We find that mutations that eliminate the visceral mesoderm expression of dpp lead to defects in midgut morphogenesis and alter the spatially localized expression of the homeotic genes Sex combs reduced (Scr), Ultrabithorax (Ubx), and Antennapedia (Antp) in the visceral mesoderm. The extracellular dpp protein migrates from the visceral mesoderm across the apposing endodermal cell layer in a region of the endoderm that expresses the homeotic gene labial (lab). Mesodermal expression of dpp is required for the expression of lab in these endodermal cells indicating that dpp mediates an inductive interaction between the two germ layers. We propose that extracellular dpp protein regulates gut morphogenesis, in part, by regulating homeotic gene expression in the visceral mesoderm and endoderm of the developing midgut.

Homeotic genes regulate the spatial expression of putative growth factors in the visceral mesoderm of Drosophila embryos

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1031-1040 ◽  
Author(s):  
R. Reuter ◽  
G.E. Panganiban ◽  
F.M. Hoffmann ◽  
M.P. Scott
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Target Genes ◽  
Transforming Growth Factor ◽  
Homeotic Genes ◽  
Visceral Mesoderm ◽  
Drosophila Embryogenesis ◽  
Growth Factor Genes ◽  
Growth Factor Beta ◽  
Drosophila Embryos

During Drosophila embryogenesis homeotic genes control the developmental diversification of body structures. The genes probably coordinate the expression of as yet unidentified target genes that carry out cell differentiation processes. At least four homeotic genes expressed in the visceral mesoderm are required for midgut morphogenesis. In addition, two growth factor homologs are expressed in specific regions of the visceral mesoderm surrounding the midgut epithelium. One of these, decapentaplegic (dpp), is a member of the transforming growth factor beta (TGF-beta) family; the other, wingless (wg), is a relative of the mammalian proto-oncogene int-1. Here we show that the spatially restricted expression of dpp in the visceral mesoderm is regulated by the homeotic genes Ubx and abd-A. Ubx is required for the expression of dpp while abd-A represses dpp. One consequence of dpp expression is the induction of labial (lab) in the underlying endoderm cells. In addition, abd-A function is required for the expression of wg in the visceral mesoderm posterior to the dpp-expressing cells. The two growth factor genes therefore are excellent candidates for target genes that are directly regulated by the homeotic genes.

scholarly journals Periadventitial Delivery of Simvastatin‐Loaded Microparticles Attenuate Venous Neointimal Hyperplasia Associated With Arteriovenous Fistula

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Chenglei Zhao ◽  
Sean T. Zuckerman ◽  
Chuanqi Cai ◽  
Sreenivasulu Kilari ◽  
Avishek Singh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Growth Factor ◽  
Kidney Disease ◽  
Arteriovenous Fistula ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Neointimal Hyperplasia ◽  
Systemic Delivery ◽  
Tgf Β1

Background Venous neointimal hyperplasia and venous stenosis (VS) formation can result in a decrease in arteriovenous fistula (AVF) patency in patients with end‐stage renal disease. There are limited therapies that prevent VNH/VS. Systemic delivery of simvastatin has been shown to reduce VNH/VS but local delivery may help decrease the side effects associated with statin use. We determined if microparticles (MP) composed of cyclodextrins loaded with simvastatin (MP‐SV) could reduce VS/VNH using a murine arteriovenous fistula model with chronic kidney disease. Methods and Results Male C57BL/6J mice underwent nephrectomy to induce chronic kidney disease. Four weeks later, an arteriovenous fistula was placed and animals were randomized to 3 groups: 20 μL of PBS or 20 μL of PBS with 16.6 mg/mL of either MP or MP‐SV. Animals were euthanized 3 days later and the outflow veins were harvested for quantitative reverse transcriptase–polymerase chain reaction analysis and 28 days later for immunohistochemistical staining with morphometric analysis. Doppler ultrasound was performed weekly. Gene expression of vascular endothelial growth factor‐A ( Vegf‐A ), matrix metalloproteinase‐9 ( Mmp‐9 ), transforming growth factor beta 1 ( Tgf‐β1 ), and monocyte chemoattractant protein‐1 ( Mcp‐1 ) were significantly decreased in MP‐SV treated vessels compared with controls. There was a significant decrease in the neointimal area, cell proliferation, inflammation, and fibrosis, with an increase in apoptosis and peak velocity in MP‐SV treated outflow veins. MP‐SV treated fibroblasts when exposed to hypoxic injury had decreased gene expression of Vegf‐A and Mmp‐9 . Conclusions In experimental arteriovenous fistulas, periadventitial delivery of MP‐SV decreased gene expression of Vegf‐A , Mmp‐9 , Tgf‐β1 and Mcp‐1, VNH/VS, inflammation, and fibrosis.

Transcriptional modulation of transin gene expression by epidermal growth factor and transforming growth factor beta

1988 ◽  
Vol 8 (6) ◽  
pp. 2479-2483
Author(s):  
C M Machida ◽  
L L Muldoon ◽  
K D Rodland ◽  
B E Magun
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Prolonged Treatment ◽  
Transcriptional Level ◽  
Tgf Beta ◽  
Epidermal Growth ◽  
Growth Factor Beta

Transin is a transformation-associated gene which is expressed constitutively in rat fibroblasts transformed by a variety of oncogenes and in malignant mouse skin carcinomas but not benign papillomas or normal skin. It has been demonstrated that, in nontransformed Rat-1 cells, transin RNA expression is modulated positively by epidermal growth factor (EGF) and negatively by transforming growth factor beta (TGF-beta); other peptide growth factors were found to have no effect on transin expression. Results presented here indicate that both protein synthesis and continuous occupancy of the EGF receptor by EGF were required for sustained induction of transin RNA. Treatment with TGF-beta inhibited the ability of EGF to induce transin, whether assayed at the transcriptional level by nuclear run-on analysis or at the level of transin RNA accumulation by Northern (RNA) blot analysis of cellular RNA. TGF-beta both blocked initial induction of transin transcription by EGF and halted established production of transin transcripts during prolonged treatment. These results suggest that TGF-beta acts at the transcriptional level to antagonize EGF-mediated induction of transin gene expression.

decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm

Development ◽  
2000 ◽  
Vol 127 (17) ◽  
pp. 3695-3702 ◽  
Author(s):  
X. Yang ◽  
M. van Beest ◽  
H. Clevers ◽  
T. Jones ◽  
D.A. Hursh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reporter Gene ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Activation ◽  
Binding Sites ◽  
Transforming Growth Factor ◽  
Ectopic Expression ◽  
Reporter Gene Expression ◽  
Enhancer Element ◽  
Visceral Mesoderm

Drosophila T cell factor (dTcf) mediates transcriptional activation in the presence of Wingless signalling and repression in its absence. Wingless signalling is required for the correct expression of decapentaplegic (dpp), a Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element, which directs expression of a reporter gene in the visceral mesoderm in a pattern indistinguishable from dpp, has two functional dTcf binding sites. Mutations that reduce or eliminate Wingless signalling abolish dpp reporter gene expression in parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless signalling components expand reporter gene expression anteriorly in the visceral mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results in ectopic expression of reporter gene expression throughout the visceral mesoderm, with no diminution of expression in the endogenous sites of expression. These results demonstrate that the primary function of dTcf binding to the dpp enhancer is repression throughout the visceral mesoderm and that activation by Wingless signalling is probably not mediated via these dTcf binding sites to facilitate correct dpp expression in the visceral mesoderm.

Sign in / Sign up

Export Citation Format

Share Document