Developmental origin of smooth muscle cells in the descending aorta in mice

Abstract

MD). R26 reporter mice (Soriano, 1999) were provided by Henrik Semb (Section of Endocrinology, Stem Cell Center, Lund University, Sweden). Animals were cross-bred to generate Hoxb6-cre/R26 reporter mice. SM22α-lacZ mice (Zhang et al., 2001) were used to track the early presence of SMC. Meox1-cre/R26 reporter mice (Jukkola et al., 2005) were used to track somite-derived cells. All transgenic lineages have a mixed genetic background. Animals were housed under barrier conditions in the transgenic core facility of University of Gothenburg, in accordance with the local ethical committee guidelines (Dnr. 213-2000, Dnr. 289-2003, Dnr. 230-2006. The morning of vaginal plug detection was counted as E0.5. Aortic smooth muscle cells (SMCs) have been proposed to derive from lateral plate mesoderm. It has further been suggested that induction of SMC differentiation is confined to the ventral side of the aorta, and that SMCs later migrate to the dorsal side. In this study, we investigate the origin of SMCs in the descending aorta using recombination-based lineage tracing in mice. Hoxb6-cre transgenic mice were crossed with Rosa 26 reporter mice to track cells of lateral plate mesoderm origin. The contribution of lateral plate mesoderm to SMCs in the descending aorta was determined at different stages of development. SMC differentiation was induced in lateral plate mesoderm-derived cells on the ventral side of the aorta at embryonic day (E) 9.0-9.5, as indicated by expression of the SMC-specific reporter gene SM22α-lacZ. There was, however, no migration of SMCs from the ventral to the dorsal side of the vessel. Moreover, the lateral plate mesoderm-derived cells in the ventral wall of the aorta were replaced by somitederived cells at E10.5, as indicated by reporter gene expression in Meox1-cre/Rosa 26 double transgenic mice. Examination of reporter gene expression in adult aortas from Hoxb6-cre/Rosa 26 and Meox1-cre/Rosa 26 double transgenic mice suggested that all SMCs in the adult descending aorta derive from the somites, whereas no contribution was recorded from lateral plate mesoderm.

Definitive human and mouse hematopoiesis originates from the embryonic endothelium: a new class of HSCs based on VE-cadherin expression

“…Thus, only the early and transient PSp/AGM mesenchymal population that gives rise to AGM aortic hemogenic endothelium has the capacity to produce HSCs progeny, and appears to do so through an endothelial intermediate. This results correlates with recent studies of aortic floor formation in both avian and murine systems (Wiegreffe et al, 2009 andPouget et al, 2008 andWasteson et al, 2008; see also Jaffredo et al, this issue) showing that the mesenchymal floor of the AGM region is transiently formed by a population derived from the lateral plate mesoderm and capable of contribution to the aortic endothelium, then replaced by a second population derived from sclerotomal mesoderm, that migrates from the dorsal and lateral walls to the ventral side of the aorta.…”

Pkd1-inactivation in vascular smooth muscle cells and adaptation to hypertension

“…This is in agreement with the early expression of endogenous SM22 and Tie2 genes, around embryonic day 8. 29,30 Our data indicate that Pkd1 gene disruption in SMCs alone and/or in ECs is not sufficient to induce gross structural abnormalities in the aorta, suggesting that additional triggers are needed to induce or to accelerate the phenotype. For the renal cystic phenotype, we previously showed that the renal injury is a trigger that strongly accelerates the polycystic kidney disease.…”

Pathologic calcification of adult vascular smooth muscle cells differs on their crest or mesodermal embryonic origin

“…(9) The rest of the aorta, that is, the entire descending aorta (including both thoracic and abdominal regions), originates from the somitic mesoderm. (10,12,13) While it is clear that remarkably sharp boundaries between these regions are set up during embryonic life, it has not been rigorously determined whether those were strictly maintained in the adult aorta. To make sure that there was no intermixing and/ or replacement of cells from one region to an adjacent region in the adult, we used Mef2c-AHF-Cre tg :R26R lacZ/þ(11) and Wnt1-Cre tg :R26R YFP/þ adult mice to analyze the fate-mapping of the ahf-and neural crest-derived VSMCs, respectively, in mice agematched with those used in our subsequent experiments.…”

“…1E), all VSMCs of the descending aorta were YFP À , confirming that they are not of neural crest origin but rather of mesodermal origin, as published for embryonic and early postnatal stages. (10,12,13) In the most proximal region of the heart, VSMCs were shown to originate from a specific embryonic mesoderm population that is the ahf. (21) In the adult, we demonstrated that this narrow region (3 to 4 mm in length) showed no sign of YFP staining on the cardiac side (Fig.…”

“…(9) On the other hand, the regions flanking both sides of the aortic arch region are of mesodermal origin. (10)(11)(12)(13) In this study we thus addressed our hypothesis by investigating the response of these distinct regions of the aorta to hyperphosphatemia, a classic stimulator of calcification, (2) by combining in vitro, ex vivo, and in vivo experiments using a mouse model deficient in matrix Gla protein (Mgp), (14) , a potent calcification inhibitor that develops extensive and spontaneous calcification of the media of the aorta. (14)(15)(16) …”