Table of Contents

Volume 6, Issue 2

  April/May/June 2010

  Pages 61 - 136

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 Issue Catalogue (MARC XML)

ORGANOGENESIS FORUM

Open Access Article

WT1 and kidney progenitor cells

Jordan A. Kreidberg
Pages 61 - 70
http://dx.doi.org/10.4161/org.6.2.11928
Abstract | PDF

Kidney development has been studied over the past sixty years as a model of embryonic induction during organogenesis. Wilms’ tumor-1 (WT1), that encodes a transcription factor and RNA-binding protein, was one of the first tumor suppressor genes identified, and was soon thereafter shown to be associated with syndromic forms of childhood kidney disease and gonadal dysgenesis. Kidney agenesis, resulting from a null mutation in the WT1 gene, was one of the first examples of organ agenesis resulting from a gene targeting experiment. Thus, the study of the WT1 gene and its encoded proteins has been at the forefront of developmental biology, tumor biology and the molecular basis for disease. WT1 is now known to have an important role in kidney progenitor cells during development. This review will discuss recent advances in our understanding of kidney progenitor cells, and the recent identification of WT1 target genes in these cells.




VIEWS AND COMMENTARY

Open Access Article

The Renal Gene Ontology Annotation Initiative

Yasmin Alam-Faruque, Emily C. Dimmer, Rachael P. Huntley, Claire O’Donovan, Peter Scambler and Rolf Apweiler
Pages 71 - 75
http://dx.doi.org/10.4161/org.6.2.11294
Abstract | PDF

The Gene Ontology (GO) resource provides dynamic controlled vocabularies to aid in the description of the functional attributes and subcellular locations of gene products from all taxonomic groups (www.geneontology.org). A renal-focused curation initiative, funded by Kidney Research UK and supported by the GO Consortium, has started at the European Bioinformatics Institute and aims to provide a detailed GO resource for mammalian proteins implicated in renal development and function. This report outlines the aims of this initiative and explains how the renal community can become involved to help improve the availability, quality and quantity of GO terms and their association to specific proteins.




REVIEWS

Open Access Article

The regulation of organ size in Drosophila : Physiology, plasticity, patterning and physical force

Alexander W. Shingleton
Pages 76 - 87
http://dx.doi.org/10.4161/org.6.2.10375
Abstract | PDF

The correct regulation of organ size is a fundamental developmental process, the failure of which can compromise organ function and organismal integrity. Consequently, the mechanisms that regulate organ size have been subject to intense research. This research has highlighted four classes of mechanism that are involved in organ size regulation: physiology, plasticity, patterning and physical force. Nevertheless, how these mechanisms are integrated and converge on the cellular process that regulate organ growth is unknown. One group of animals where this integration is beginning to be achieved is in the insects. Here, I review the different mechanisms that regulate organ size in insects, and describe our current understanding of how these mechanisms interact. The genes and hormones involved are remarkably conserved in all animals, so these studies in insects provide a precedent for future research on organ size regulation in mammals.

Open Access Article

Scaling properties of cell and organelle size

Yee-Hung M. Chan and Wallace F. Marshall
Pages 88 - 96
http://dx.doi.org/10.4161/org.6.2.11464
Abstract | PDF

How size is controlled is a fundamental question in biology. In this review, we discuss the use of scaling relationships—for example, power laws of the form y ∝ xα—to provide a framework for comparison and interpretation of size measurements. Such analysis can illustrate the biological and physical principles underlying observed trends, as has been proposed for the allometric dependence of metabolic rate or limb structure on organism mass. Techniques for measuring size at smaller length-scales continue to improve, leading to more data on the control of size in cells and organelles. Size scaling of these structures is expected to influence growth patterns, functional capacity, and intracellular transport. Furthermore, organelles such as the nucleus, mitochondria, and endoplasmic reticulum show widely varying morphologies which affect their scaling properties. We provide brief summaries of these issues for individual organelles, and conclude with a discussion on how to apply this concept to better understand the mechanisms of size control in the cellular environment.

Open Access Article

VEGF receptor signaling in vertebrate development

Joaquim Miguel Vieira, Christiana Ruhrberg and Quenten Schwarz
Pages 97 - 106
http://dx.doi.org/10.4161/org.6.2.11686
Abstract | PDF

The secreted glycoprotein vascular endothelial growth factor A (VEGF or VEGFA) affects many different cell types and modifies a wide spectrum of cellular behaviors in 
tissue culture models, including proliferation, migration, differentiation and survival. The versatility of VEGF signaling is reflected in the complex composition of its cell surface receptors and their ability to activate a variety of different downstream signaling molecules. A major challenge for VEGF research is to determine which of the specific signaling pathways identified in vitro control development and homeostasis of tissues containing VEGF-responsive cell types in vivo.

Note: Previously published in VEGF in Development, edited by Christiana Ruhrberg. Landes Bioscience and Springer Science+Business Media 2008; pp. 14-29.

Open Access Article

VEGF in the nervous system

Jeffrey M. Rosenstein, Janette M. Krum and Christiana Ruhrberg
Pages 107 - 114
http://dx.doi.org/10.4161/org.6.2.11687
Abstract | PDF

Vascular endothelial growth factor (VEGF, VEGFA) is critical for blood vessel growth in 
the developing and adult nervous system of vertebrates. Several recent studies demonstrate that VEGF also promotes neurogenesis, neuronal patterning, neuroprotection and glial growth. For example, VEGF treatment of cultured neurons enhances survival and neurite growth independently of blood vessels. Moreover, evidence is emerging that VEGF guides neuronal migration in the embryonic brain and supports axonal and arterial co-patterning in the developing skin. Even though further work is needed to understand the various roles of VEGF in the nervous system and to distinguish direct neuronal effects from indirect, vessel-mediated effects, VEGF can be considered a promising tool to promote neuronal health and nerve repair.


Note: Previously published in VEGF in Development, edited by Christiana Ruhrberg. Landes Bioscience and Springer Science+Business Media 2008; pp. 91-103.




RESEARCH PAPERS

Open Access Article

Reduction of diffusion barriers in isolated rat islets improves survival, but not insulin secretion or transplantation outcome

S. Janette Williams, Han-Hung Huang, Karen Kover, Wayne V. Moore, Cory Berkland, Milind Singh, Irina S. Smirnova, Ronal MacGregor and Lisa Stehno-Bittel
Pages 115 - 124
http://dx.doi.org/10.4161/org.6.2.10373
Abstract | PDF

For people with type 1 diabetes and severe hypoglycemic unawareness, islet transplants offer hope for improving the quality of life. However, islet cell death occurs quickly during or after transplantation, requiring large quantities of islets per transplant. The purpose of this study was to determine whether poor function demonstrated in large islets was a result of diffusion barriers and if removing those barriers could improve function and transplantation outcomes. Islets were isolated from male DA rats and measured for cell viability, islet survival, glucose diffusion and insulin secretion. Modeling of diffusion barriers was completed using dynamic partial differential equations for a sphere. Core cell death occurred in 100% of the large islets (diameter > 150 μm), resulting in poor survival within 7 days after isolation. In contrast, small islets (diameter < 100 μm) exhibited good survival rates in culture (91%). Glucose diffusion into islets was tracked with 2-NBDG; 4.2 μm/min in small islets and 2.8 μm/min in large islets. 2-NBDG never permeated to the core cells of islets larger than 150μm diameter. Reducing the diffusion barrier in large islets improved their immediate and long-term viability in culture. However, reduction of the diffusion barrier in large islets failed to improve their inferior in vitro insulin secretion compared to small islets, and did not return glucose control to diabetic animals following transplantation. Thus, diffusion barriers lead to low viability and poor survival for large islets, but are not solely responsible for the inferior insulin secretion or poor transplantation outcomes of large versus small islets.

Open Access Article

Non-β-cell progenitors of β-cells in pregnant mice

Sylvie Abouna, Robert W. Old, Stella Pelengaris, David Epstein, Vasiliki Ifandi, Ian Sweeney and Michael Khan
Pages 125 - 133
http://dx.doi.org/10.4161/org.6.2.10374
Abstract | PDF

Pregnancy is a normal physiological condition in which the maternal β-cell mass increases rapidly about two-fold to adapt to new metabolic challenges. We have used a lineage tracing of β-cells to analyse the origin of new β-cells during this rapid expansion in pregnancy. Double transgenic mice bearing a tamoxifen-dependent Cre-recombinase construct under the control of a rat insulin promoter, together with a reporter Z/AP gene, were generated. Then, in response to a pulse of tamoxifen before pregnancy, β-cells in these animals were marked irreversibly and heritably with the human placental alkaline phosphatase (HPAP). First, we conclude that the lineage tracing system was highly specific for β-cells. Secondly, we scored the proportion of the β-cells marked with HPAP during a subsequent chase period in pregnant and non-pregnant females. We observed a dilution in this labelling index in pregnant animal pancreata, compared to non-pregnant controls, during a single pregnancy in the chase period. To extend these observations we also analysed the labelling index in pancreata of animals during the second of two pregnancies in the chase period. The combined data revealed statistically-significant dilution during pregnancy, indicating a contribution to new beta cells from a non-β-cell source. Thus for the first time in a normal physiological condition, we have demonstrated not only β-cell duplication, but also the activation of a non-β-cell progenitor population. Further, there was no transdifferentiation of β-cells to other cell types in a two and half month period following labelling, including the period of pregnancy.

Open Access Article

Method for the decellularization of intact rat liver

Thomas Shupe, Matthew Williams, Alicia Brown, Bradley Willenberg and Bryon E. Petersen
Pages 134 - 136
http://dx.doi.org/10.4161/org.6.2.11546
Abstract | PDF

We have developed a method for the decellularization of whole rat livers by perfusion with increasing concentrations of detergents. This procedure resulted in an intact, decellularized organ with an intact liver capsule. These decellularized organs were analyzed by immunohistochemistry, and retained an appropriate distribution of extracellular matrix components. The laminin basement membranes of the liver vasculature also remain intact. These acellular vessel remnants were strong enough to be cannulated; providing a convenient means for the delivery of cells to areas deep within the decellularized organ. Cannulation of the extrahepatic vessel remnants allow for media to be circulated through the decellularized organ. These decellularized livers provide a natural matrix for research in the fields of bio-artificial livers and liver engineering.