GSE128378
Lyl-1 links primitive macrophages and microglia development to neuropsychiatric disorders
The regulation of developmental haematopoiesis by the bHLH transcription factor Lyl-1 has been the focus of our present study. Analysing how Lyl-1 may impact mouse developmental haematopoiesis indicated that Lyl-1 marks YS-derived primitive macrophage progenitors, as well as embryonic microglia. During ontogeny, microglia which representtissue macrophages of the central nervous system emerge from haematopoietic stem cell-independent progenitors originating from the yolk sac (YS). Activation of microglia during development is often critical and my lead to neuropsychiatric diseases in the adult. Here, we show that Lyl-1 disruption alters the development of microglia with far reaching consequences. Lyl-1-deficiency leads to decreased dendritic spine density and impaired neuronal activity, as well as impaired social interactions with increased anxiety-like behaviour. We thus identify Lyl-1 as a critical regulator of primitive macrophage and microglia development, whose disruption impacts microglia development and functionality, leading to a distinct neuropsychiatric phenotype. Overall design: Analyses of microglia from wt and Lyl1ko mice