Identification of a novel developmental mechanism in the generation of mesothelia

Abstract

SUMMARYMesothelium is the surface layer of all coelomic organs and is crucial for the generation of their vasculature. Still, our understanding of the genesis of this essential cell type is restricted to the heart where a localized exogenous population of cells, the proepicardium, migrates to and envelops the myocardium supplying mesothelial, vascular and stromal cell lineages. Currently it is not known whether this pattern of development is specific to the heart or applies broadly to other coelomic organs. Using two independent long-term lineage-tracing studies, we demonstrate that mesothelial progenitors of the intestine are intrinsic to the gut tube anlage. Furthermore, a novel chick-quail chimera model of gut morphogenesis reveals these mesothelial progenitors are broadly distributed throughout the gut primordium and are not derived from a localized and exogenous proepicardium-like source of cells. These data demonstrate an intrinsic origin of mesothelial cells to a coelomic organ and provide a novel mechanism for the generation of mesothelial cells.

Resident progenitors, not exogenous migratory cells, generate the majority of visceral mesothelium in organogenesis

“…To our surprise, we instead determined that unlike the heart, the avian intestinal splanchnic mesoderm housed broadly distributed mesothelial progenitors that differentiated in situ rather than from an external migratory population. This provided the first experimental evidence of an alternative model of mesothelial formation (19). …”

“…However, it is unknown whether the mechanisms of cardiac mesotheliogenesis, in particular the requirement to recruit exogenous mesothelial cell progenitors to the developing organ, are applied broadly throughout vertebrate organogenesis. We recently reported the intestine employed an alternative mechanism of mesothelial formation – generation of mesothelium from a broadly-distributed intrinsic population of progenitors (19). Still, the question remains as to whether a major conserved mechanism in this process is observed.…”

Establishment of the Visceral Embryonic Midline Is a Dynamic Process that Requires Bilaterally Symmetric BMP Signaling

“…The CE Generates the Mesenchyme of the DM and Subaortic Region by Epithelial-to-Mesenchymal Transition The appearance of mesenchymal cells during formation of the DM, together with observations of other groups (Gros and Tabin, 2014;Richard et al, 2013;Winters et al, 2012;Winters et al, 2014), suggested that epithelial-to-mesenchymal transition (EMT) of the CE may be important for formation of the DM and ventral mesenchyme. To explore this possibility, we performed fate mapping by electroporating a constitutive GFP-expressing plasmid into the CE on one side of the embryo ( Figure 1K).…”

A Subset of Malignant Mesothelioma Tumors Retain Osteogenic Potential

“…During development, mesothelium lining the heart, liver, lungs and gut differentiate into vascular smooth muscle cells, interstitial fibroblasts, hepatic stellate cells, endothelial cells and adipocytes323334353637. More recently, adult mesothelial cells have also been shown to undergo MMT and differentiate into vascular smooth muscle cells, adipocytes and osteoblasts43839 and are likely to play important roles in fibrogenesis40.…”