Acute Response and Neuroprotective Role of Myo/Nog Cells Assessed in a Rat Model of Focal Brain Injury.

Focal brain injury in the form of a needlestick (NS) results in cell death and induces a self-protective response flanking the lesion. Myo/Nog cells are identified by their expression of bone morphogenetic protein inhibitor Noggin, brain-specific angiogenesis inhibitor 1 (BAI1) and the skeletal muscle specific transcription factor MyoD. Myo/Nog cells limit cell death in two forms of retinopathy. In this study, we examined the acute response of Myo/Nog cells to a NS lesion that extended from the rat posterior parietal cortex to the hippocampus. Myo/Nog cells were identified with antibodies to Noggin and BAI1. These cells were the primary source of both molecules in the uninjured and injured brain. One day after the NS, the normally small population of Myo/Nog cells expanded approximately eightfold within a 1 mm area surrounding the lesion. Myo/Nog cells were reduced by approximately 50% along the lesion with an injection of the BAI1 monoclonal antibody and complement. The number of dying cells, identified by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), was unchanged at this early time point in response to the decrease in Myo/Nog cells. However, increasing the number of Myo/Nog cells within the lesion by injecting BAI1-positive (+) cells isolated from the brains of other animals, significantly reduced cell death and increased the number of NeuN+ neurons compared to brains injected with phosphate buffered saline or exogenous BAI1-negative cells. These findings demonstrate that Myo/Nog cells rapidly react to injury within the brain and increasing their number within the lesion is neuroprotective.

Myo/Nog cells are nonprofessional phagocytes.

Myo/Nog cells were discovered in the chick embryo epiblast. Their expression of MyoD reflects a commitment to the skeletal muscle lineage and capacity to differentiate into myofibroblasts. Release of Noggin by Myo/Nog cells is essential for normal morphogenesis. Myo/Nog cells rapidly respond to wounding in the skin and eyes. In this report, we present evidence suggesting that Myo/Nog cells phagocytose tattoo ink in tissue sections of human skin and engulf cell corpses in cultures of anterior human lens tissue and magnetic beads injected into the anterior chamber of mice in vivo. Myo/Nog cells are distinct from macrophages in the skin and eyes indicated by the absence of labeling with an antibody to ionized calcium binding adaptor molecule 1. In addition to their primary roles as regulators of BMP signaling and progenitors of myofibroblasts, Myo/Nog cells behave as nonprofessional phagocytes defined as cells whose primary functions are unrelated to phagocytosis but are capable of engulfment.