TY - JOUR T1 - Atypical cadherin FAT3 is a novel mediator for morphological changes of microglia JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0056-20.2020 SP - ENEURO.0056-20.2020 AU - Tomomi Okajima AU - Yichen Gu AU - Rin-ichiro Teruya AU - Sarasa Yano AU - Takumi Taketomi AU - Ban Sato AU - Tomoki Chiba AU - Fuminori Tsuruta Y1 - 2020/08/31 UR - http://www.eneuro.org/content/early/2020/08/28/ENEURO.0056-20.2020.abstract N2 - Microglia are resident macrophages, which are critical for brain development and homeostasis. Microglial morphology is dynamically changed during postnatal stages, leading to regulating synaptogenesis and synapse pruning. Moreover, it has been well known that the shape of microglia is also altered in response to the detritus of the apoptotic cells and pathogens such as bacteria and viruses. Although the morphological changes are crucial for acquiring microglial functions, the exact mechanism which controls their morphology is not fully understood. Here we report that the FAT atypical cadherin family protein, FAT3, regulates the morphology of microglial cell line, BV2. We found that the shape of BV2 becomes elongated in a high nutrient medium. Using microarray analysis, we identified that FAT3 expression is induced by culturing with a high nutrient medium. In addition, we found that purinergic analog, hypoxanthine, promotes FAT3 expression in BV2 and mouse primary microglia. FAT3 expression induced by hypoxanthine extends the time of sustaining the elongated forms in BV2. These data suggest that the hypoxanthine-FAT3 axis is a novel pathway associated with microglial morphology. Our data provide a possibility that FAT3 may control microglial transitions involved in their morphological changes during the postnatal stages in vivo.Significance Statement Microglia play an important role in regulating neural circuit formation and brain homeostasis. Microglial morphology is greatly changed from reactive form to surveillant form after birth. Intriguingly, these morphological changes are tightly associated with regulating higher brain functions. However, the mechanisms of morphological changes have not been elucidated. Here, we report that atypical cadherin family protein, FAT3, is a novel regulator for microglial morphology. We found that FAT3 expression is induced by purinergic derivative, hypoxanthine, and is necessary for sustaining microglial morphology after changing to elongated shapes in vitro. Because both purinergic metabolism and FAT3 pathway have been implicated in neurodevelopmental disorders, our findings may shed light on the novel approach for treating these disorders associated with a microglial abnormality. ER -