The mesothelium is an epithelial structure derived from the embryonic mesoderm. It plays an important role in the development of a number of different organs, including the heart, lungs, and intestines. In this publication, we discuss aspects of the development of the mesothelium, where mesothelial structures can be found, and review molecular and cellular characteristics associated with the mesothelium. Furthermore, we discuss the involvement of the mesothelium in a number of disease conditions, in particular in the pathogenesis of mesotheliomas with an emphasis on malignant pleural mesothelioma (MPM)—a primary cancer developing in the pleural cavity.

Host genetic factors are thought to contribute to the interindividual differences in the control of HIV replication. The aim of the present investigation was to determine whether genes encoding GM and KM allotypes—genetic markers of immunoglobulin γ and κ chains, respectively—and those encoding Fcgamma receptor (FcγR) IIa and IIIa are associated with the host control of HIV replication. A case-control design was employed amongst HIV-infected subjects, with a group that spontaneously controlled HIV replication (“controllers”) as cases (n=73) and those who did not control replication, as controls (n=100). Genotyping was done by PCR-RFLP, direct DNA sequencing, and TaqMan® genotyping assays. In Caucasian Americans, certain combinations of FcγR and GM genotypes were differentially distributed between controllers and non-controllers. Among the non-carriers of FcγRIIa arginine allele, GM21 non-carriers had over seven-fold greater odds of being controllers than the carriers of this allele (OR=7.47). These GM determinants also interacted with FcγRIIIa alleles. Among the carriers of the FcγRIIIa valine allele, GM21 non-carriers had over three-fold greater odds of being controllers than the carriers of this allele (OR=3.26). These results show epistatic interactions of genes on chromosomes 14 (GM) and 1 (FcγR) in influencing the control of HIV replication.

Primary cilia are small organelles projecting from the cell surface of various cell types. They play a crucial role in the regulation of various signaling pathway. In this study, we investigated the importance of cilia for heart development by conditionally deleting intraflagellar transport protein Ift88 using the col3.6-cre mouse. Analysis of col3.6;Ift88 offspring showed a wide spectrum of cardiovascular defects including Double Outlet Right Ventricle and Atrioventricular Septal Defects. In addition, we found that in the majority of specimens the pulmonary veins did not properly connect to the developing left atrium. The abnormal connections found resemble those seen in patients with Total Anomalous Pulmonary Venous Return. Analysis of mutant hearts at early stages of development revealed abnormal development of the dorsal mesocardium, a second heart field-derived structure at the venous pole intrinsically related to the development of the pulmonary veins. Data presented support a crucial role for primary cilia in outflow tract development and atrioventricular septation and their significance for the formation of the second heart field derived tissues at the venous pole including the dorsal mesocardium. Furthermore, the results of this study indicate that proper formation of the dorsal mesocardium is critically important for the development of the pulmonary veins.

Failure to form the septal structures that separate the left and right cardiac chambers results in defects that allow shunting of blood from one side of the heart to the other, leading to the mixing of oxygenated and de-oxygenated blood. The atrioventricular (AV) mesenchymal complex, consisting of the AV cushions, the Dorsal Mesenchymal Protrusion (DMP), and the mesenchymal cap, plays a crucial role in AV septation. Cells found in these structures derive from different cell lineages. In this study we have investigated the role of the transcription factor Sox9 in the Second Heart Field (SHF) with the emphasis on the formation of the atrioventricular septal complex. Using a mouse model in which Sox9 is conditionally deleted from the SHF we demonstrate that in this model virtually all mouse embryos develop septal abnormalities, including complete atrioventricular septal defects (cAVSDs) and isolated ventricular septal defects. Our morphological analyses indicate that perturbation of the development of the mesenchymal cap appears to play a crucial role in the pathogenesis of the atrial septal defects observed in the AVSDs and suggests that this component of the AV mesenchymal complex might play a more important role in AV septation than previously appreciated.

No abstract