Defective vascular development in connexin 45-deficient mice

Development ◽  
2000 ◽  
Vol 127 (19) ◽  
pp. 4179-4193 ◽  
Author(s):  
O. Kruger ◽  
A. Plum ◽  
J.S. Kim ◽  
E. Winterhager ◽  
S. Maxeiner ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Reporter Gene ◽  
Vascular Development ◽  
Subsequent Development ◽  
Yolk Sac ◽  
Abnormal Development ◽  
Coding Region ◽  
Junction Protein ◽  
Visceral Smooth Muscle ◽  
Deficient Mice

In order to reveal the biological function(s) of the gap-junction protein connexin 45 (Cx45), we generated Cx45-deficient mice with targeted replacement of the Cx45-coding region with the lacZ reporter gene. Heterozygous Cx45(+/)(−) mice showed strong expression of the reporter gene in vascular and visceral smooth muscle cells. Cx45-deficient embryos exhibited striking abnormalities in vascular development and died between embryonic day (E) 9.5 and 10.5. Differentiation and positioning of endothelial cells appeared to be normal, but subsequent development of blood vessels revealed impaired formation of vascular trees in the yolk sac, impaired allantoic mesenchymal ingrowth and capillary formation in the labyrinthine part of the placenta, and arrest of arterial growth, including a failure to develop a smooth muscle layer surrounding the major arteries of the embryo proper. As a consequence, the hearts of most Cx45-deficient embryos were dilated. The abnormal development of the vasculature in the yolk sac of Cx45(−)(/)(−) embryos could be caused by defective TGFbeta signalling, as the amount of TGF beta1 protein in the epithelial layer of the yolk sac was largely decreased in the E9.5 Cx45(−)(/)(−) embryo, compared with the wild-type embryo. The defective vascular development was accompanied by massive apoptosis, which began in some embryos at E8.5 and was abundant in virtually all tissues of the embryos at E9.5. We conclude that in Cx45(−)(/)(−) embryos, vasculogenesis was normal, but subsequent transformation into mature vessels was interrupted. Development of different types of vessels was impaired to a varying extent, which possibly reflects the complementation by other connexin(s).

Wnt7b regulates mesenchymal proliferation and vascular development in the lung

Development ◽  
2002 ◽  
Vol 129 (20) ◽  
pp. 4831-4842 ◽  
Author(s):  
Weiguo Shu ◽  
Yue Qin Jiang ◽  
Min Min Lu ◽  
Edward E. Morrisey
Keyword(s):  
Smooth Muscle ◽  
Airway Epithelium ◽  
Lung Development ◽  
Perinatal Death ◽  
Vascular Development ◽  
Wnt Signaling Pathway ◽  
Lung Hypoplasia ◽  
Coding Region ◽  
Newborn Mice ◽  
Pulmonary Vessels

Although the Wnt signaling pathway regulates inductive interactions between epithelial and mesenchymal cells, little is known of the role that this pathway plays during lung development. Wnt7b is expressed in the airway epithelium, suggesting a possible role for Wnt-mediated signaling in the regulation of lung development. To test this hypothesis, we have mutated Wnt7b in the germline of mice by replacement of the first exon with the lacZ-coding region. Wnt7blacZ–/– mice exhibit perinatal death due to respiratory failure. Defects in early mesenchymal proliferation leading to lung hypoplasia are observed in Wnt7blacZ–/– embryos. In addition, Wnt7blacZ–/– embryos and newborn mice exhibit severe defects in the smooth muscle component of the major pulmonary vessels. These defects lead to rupture of the major vessels and hemorrhage in the lungs after birth. These results demonstrate that Wnt7b signaling is required for proper lung mesenchymal growth and vascular development.

NH2-terminal-inserted myosin II heavy chain is expressed in smooth muscle of small muscular arteries

1997 ◽  
Vol 272 (5) ◽  
pp. C1532-C1542 ◽  
Author(s):  
M. E. DiSanto ◽  
R. H. Cox ◽  
Z. Wang ◽  
S. Chacko
Keyword(s):  
Smooth Muscle ◽  
Atpase Activity ◽  
Heavy Chain ◽  
Light Chain ◽  
Maximum Velocity ◽  
Myosin Isoforms ◽  
Coding Region ◽  
Shortening Velocity ◽  
Visceral Smooth Muscle ◽  
Saphenous Artery

We demonstrate, using reverse transcriptase-polymerase chain reaction, that, whereas abdominal aorta from rabbit consists almost entirely of myosin heavy chain (MHC) mRNA with no insert at the 5'-terminal coding region, the distributing arteries (femoral and saphenous) begin to show MHC mRNA with the 21-nucleotide insert that encodes seven amino acids in the ATP-binding region located in the myosin head. The femoral/iliac artery contains > 50% inserted mRNA, whereas the more distal saphenous artery contains > 80% inserted mRNA. This insert is also present in the smooth muscle from rat tail artery but is absent in the smooth muscle from rat aorta. The actin-activated ATPase activity of myosin from the rabbit femoral/saphenous artery is 1.7-fold higher than that of the myosin from the aorta. A concomitant increase (about twofold) in the maximum shortening velocity of the saphenous artery, compared with that of the aorta, indicates that the preponderance of the inserted myosin is associated with both an increase in the actin-activated ATPase activity and a larger maximum velocity of shortening. Furthermore, analysis of the 17-kDa essential light chain from the aorta reveals near equal quantities of the 17-kDa light chain isoforms a and b, whereas the myosin from the femoral/ saphenous artery contains predominantly the 17-kDa light chain a isoform. Together, these data indicate that the smooth muscle cells from the small distributing arteries are similar to those of visceral smooth muscle with respect to the expression of myosin isoforms, actin-activated myosin ATPase activity and contractility.

An SCL +19 Core Enhancer Targets Three Mesoderm-Derived Cell Lineages - Blood, Endothelium and Smooth Muscle.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4200-4200
Author(s):  
Lev Silberstein ◽  
Maria Jose Sanchez ◽  
Merav Socolovsky ◽  
Gary J. Hoffman ◽  
Sandie Piltz ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Smooth Muscle ◽  
Mast Cells ◽  
Reporter Gene ◽  
Cell Leukaemia ◽  
Placental Alkaline Phosphatase ◽  
Haematopoietic Stem Cells ◽  
Foetal Liver ◽  
Visceral Smooth Muscle

Abstract The stem cell leukaemia (SCL) gene encodes a basic helix-loop-helix transcription factor with a critical role in normal haematopoiesis and angiogenesis. The SCL gene is normally expressed in haematopoietic stem cells, mast cells, megakaryocytes, endothelium and smooth muscle. Aberrant expression of the SCL gene leads to T-cell acute lymphoblastic leukaemia, whereas SCL−/− mice die due to the absence of haematopoiesis. Hence, temporal and spatial regulation of SCL expression is essential. Our laboratory has previously characterised a 5.5 kb enhancer located 3′ of the SCL transcription start site, which is capable of targeting expression of b-galactozidase (LacZ) reporter gene to haematopoietic stem cells in the foetal liver and the bone marrow, as well as embryonic endothelium. Subsequent experiments showed that a 641-base pair core enhancer gave an identical pattern of lacZ expression in the embryo. However, it was unclear if the same element (later referred to as +19 core enhancer) was capable of maintaining reporter gene expression into the adulthood, since no lacZ activity was observed in postnatal mice. Using a transgenic construct containing a eukaryotic reporter gene, human placental alkaline phosphatase, we show that in the haematopoietic system, the +19 core enhancer is sufficient to target foetal liver and bone marrow HSCs, as well as mast cells and megakaryocytes. In the erythroid lineage, the enhancer is active only during the earlier stages of erythropoiesis, despite high level of SCL expression throughout erythroblast maturation, suggesting that an additional element is likely to be required to maintain SCL expression. The enhancer also targets embryonic and adult endothelium, together with vascular and visceral smooth muscle. Taken together, our results demonstrate that the 641-bp +19 core enhancer is sufficient to integrate signals upstream of SCL in blood, endothelium and smooth muscle. Our data also suggest that developmental relationship between these three mesoderm-derived lineages could be defined through a common transcriptional environment, and indicate that SCL may play a wider role in mesodermal development than previously thought.

scholarly journals The PIAS-Like Protein Zimp10 Is Essential for Embryonic Viability and Proper Vascular Development

2007 ◽  
Vol 28 (1) ◽  
pp. 282-292 ◽  
Author(s):  
Jason Beliakoff ◽  
Jane Lee ◽  
Hiroo Ueno ◽  
Aparna Aiyer ◽  
Irving L. Weissman ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Vascular Development ◽  
Yolk Sac ◽  
Vascular Plexus ◽  
Reverse Transcription Pcr ◽  
Chromatin Remodeling Complexes ◽  
Transcriptional Coregulator ◽  
Deficient Mice ◽  
Embryonic Viability

ABSTRACT Members of the PIAS (for protein inhibitor of activated STAT) family play critical roles in modulating the activity of a variety of transcriptional regulators. Zimp10, a novel PIAS-like protein, is a transcriptional coregulator and may be involved in the modification of chromatin through interactions with the SWI/SNF chromatin-remodeling complexes. Here, we investigate the biological role of Zimp10 in zimp10-deficient mice. Homozygosity for the Zimp10-targeted allele resulted in developmental arrest at approximately embryonic day 10.5. Analysis of knockout embryos revealed severe defects in the reorganization of the yolk sac vascular plexus. No significant abnormality in hematopoietic potential was observed in zimp10 null mice. Microarray and quantified reverse transcription-PCR analyses showed that the expression of the Fos family member Fra-1, which is involved in extraembryonic vascular development, was reduced in yolk sac tissues of zimp10 null embryos. Using fra-1 promoter/reporter constructs, we further demonstrate the regulatory role of Zimp10 on the transcription of Fra-1. This study provides evidence to demonstrate a crucial role for Zimp10 in vasculogenesis.

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