24 research outputs found
Endothelial cells regulate neural crest and second heart field morphogenesis
Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio–craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1) in the mesoderm results in early embryonic lethality, severe deformation of the cardio–craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1) along with changes in the extracellular matrix (ECM) composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio–craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1
Loss of Muscle MTCH2 Increases Whole-Body Energy Utilization and Protects from Diet-Induced Obesity
SummaryMitochondrial carrier homolog 2 (MTCH2) is a repressor of mitochondrial oxidative phosphorylation (OXPHOS), and its locus is associated with increased BMI in humans. Here, we demonstrate that mice deficient in muscle MTCH2 are protected from diet-induced obesity and hyperinsulinemia and that they demonstrate increased energy expenditure. Deletion of muscle MTCH2 also increases mitochondrial OXPHOS and mass, triggers conversion from glycolytic to oxidative fibers, increases capacity for endurance exercise, and increases heart function. Moreover, metabolic profiling of mice deficient in muscle MTCH2 reveals a preference for carbohydrate utilization and an increase in mitochondria and glycolytic flux in muscles. Thus, MTCH2 is a critical player in muscle biology, modulating metabolism and mitochondria mass as well as impacting whole-body energy homeostasis
Loss of Ptpn11 (Shp2) drives satellite cells into quiescence
The equilibrium between proliferation and quiescence of myogenic progenitor
and stem cells is tightly regulated to ensure appropriate skeletal muscle
growth and repair. The non-receptor tyrosine phosphatase Ptpn11 (Shp2) is an
important transducer of growth factor and cytokine signals. Here we combined
complex genetic analyses, biochemical studies and pharmacological interference
to demonstrate a central role of Ptpn11 in postnatal myogenesis of mice. Loss
of Ptpn11 drove muscle stem cells out of the proliferative and into a resting
state during muscle growth. This Ptpn11 function was observed in postnatal but
not fetal myogenic stem cells. Furthermore, muscle repair was severely
perturbed when Ptpn11 was ablated in stem cells due to a deficit in stem cell
proliferation and survival. Our data demonstrate a molecular difference in the
control of cell cycle withdrawal in fetal and postnatal myogenic stem cells,
and assign to Ptpn11 signaling a key function in satellite cell activity
Recommended from our members
Endothelial cells regulate neural crest and second heart field morphogenesis.
Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio-craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1) in the mesoderm results in early embryonic lethality, severe deformation of the cardio-craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1) along with changes in the extracellular matrix (ECM) composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio-craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1
Endothelial cells regulate neural crest and second heart field morphogenesis.
Cardiac and craniofacial developmental programs are intricately linked during early embryogenesis, which is also reflected by a high frequency of birth defects affecting both regions. The molecular nature of the crosstalk between mesoderm and neural crest progenitors and the involvement of endothelial cells within the cardio-craniofacial field are largely unclear. Here we show in the mouse that genetic ablation of vascular endothelial growth factor receptor 2 (Flk1) in the mesoderm results in early embryonic lethality, severe deformation of the cardio-craniofacial field, lack of endothelial cells and a poorly formed vascular system. We provide evidence that endothelial cells are required for migration and survival of cranial neural crest cells and consequently for the deployment of second heart field progenitors into the cardiac outflow tract. Insights into the molecular mechanisms reveal marked reduction in Transforming growth factor beta 1 (Tgfb1) along with changes in the extracellular matrix (ECM) composition. Our collective findings in both mouse and avian models suggest that endothelial cells coordinate cardio-craniofacial morphogenesis, in part via a conserved signaling circuit regulating ECM remodeling by Tgfb1
Concise Review: The Deleterious Effects of Cigarette Smoking and Nicotine Usage and Mesenchymal Stem Cell Function and Implications for Cell-Based Therapies
Stem cell sources for cell-based therapeutics are often screened for infectious agents and genetic diseases prior to implantation; however, there are other risk factors that are often overlooked, which may ultimately lead to less efficacious clinical outcomes. One such risk factor is exposure of mesenchymal stem cells (MSCs) to cigarette smoke or nicotine. Recent data have shown that exposure to cigarette smoke or nicotine leads to decreased regenerative potential, namely decreased proliferation, decreased migration, and decreased differentiation potential of exposed MSCs. This review provides a brief introduction into MSCs and their respective niches and a summary regarding the interactions of cigarettes and nicotine with MSCs populations. Specifically, the effects of cigarette smoke and nicotine on the regenerative potential of MSCs (i.e., proliferation, migration, and differentiation) will be covered with an emphasis on considerations for the development of future cell-based clinical trials and therapies. Stem Cells Translational Medicine 2017;6:1815-1821