Morphofunctional programming of microglia requires distinct roles of type II myosins.

The ramified morphology of microglia and the dynamics of their membrane protrusions are essential for their functions in central nervous system development, homeostasis, and disease. Although their ability to change and control shape critically depends on the actin and actomyosin cytoskeleton, the underlying regulatory mechanisms remain largely unknown. In this study, we systematically analyzed the actomyosin cytoskeleton and regulators downstream of the small GTPase RhoA in the control of microglia shape and function. Our results reveal that (i) Myh9 controls cortical tension levels and affects microglia protrusion formation, (ii) cofilin-mediated maintenance of actin turnover regulates microglia protrusion extension, and (iii) Myh10 influences microglia inflammatory activation. Overall we uncover molecular pathways that regulate microglia morphology and identify type-II myosins as important regulators of microglia biology with differential roles in the control of cell shape (Myh9) and functions (Myh10).

Altered oxygen metabolism associated to neurogenesis of induced pluripotent stem cells derived from a schizophrenic patient.

Schizophrenia has been defined as a neurodevelopmental disease that causes changes in the process of thoughts, perceptions, and emotions, usually leading to a mental deterioration and affective blunting. Studies have shown altered cell respiration and oxidative stress response in schizophrenia; however, most of the knowledge has been acquired from postmortem brain analyses or from nonneural cells. Here we describe that neural cells, derived from induced pluripotent stem cells generated from skin fibroblasts of a schizophrenic patient, presented a twofold increase in extramitochondrial oxygen consumption as well as elevated levels of reactive oxygen species (ROS), when compared to controls. This difference in ROS levels was reverted by the mood stabilizer valproic acid. Our model shows evidence that metabolic changes occurring during neurogenesis are associated with schizophrenia, contributing to a better understanding of the development of the disease and highlighting potential targets for treatment and drug screening.