Function of Thy-1 (CD90) in the neuron – astrocyte communication

• Applicant: Privatdozentin Dr. Anja Saalbach
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 464383417

Thy-1 (CD90) is a cell surface molecule expressed on activated microvascular endothelial cells, fibroblasts, mesenchymal stem cells (MSC), and mature neurons. Previously, we identified Thy-1 as an activation-dependent cell adhesion molecule on microvascular endothelial cells. In fibroblasts, we demonstrated that Thy-1 controls the balance between proliferation and apoptosis as well as the differentiation of fibroblasts to myofibroblasts. Finally, we identified Thy-1 as a regulator molecule on MSC that promotes osteogenesis and thus bone formation while inhibiting adipogenesis and obesity. While the Thy-1 promoter is well known and widely used as a neuron-specific promoter for transgenic expression in projections neurons, the function of the endogenous Thy-1 protein highly expressed on neurons has remained enigmatic so far. Neurons are integrated in a complex network of astrocytes, microglia and oligodendrocytes. Communication of astrocytes and neurons regulates homeostasis of the extracellular milieu, brain metabolism, cerebral microcirculation and the blood brain barrier. During injury, astrocytes get activated from a normal functional, “quiescent” state and change many of their properties, a process called astrogliosis. Essential functions of astrogliosis include the protection of neural cells, the restriction of inflammation and infection, and the preservation of tissue and function. In contrast, persistent reactive astrogliosis can be harmful due to inhibition of axonal regeneration.Thy-1 is highly expressed on neurons, several potential receptors are expressed on astrocytes and Thy-1 binds to the astrocytic surface. Importantly, astrocytes express signs of activation when Thy-1 is lacking on neurons in the absence of neurodegeneration. Therefore, we hypothesize that Thy-1 contributes to signaling from neurons to astrocytes and that this signaling keeps astrocytes in a quiescent state.In the present project, we therefore aim at elucidating the role of Thy-1 in neuron-astrocyte communication under physiological and pathophysiological conditions. By analysis of astrocytes in mice with a neuron-specific deletion of Thy-1 compared to wildtype mice we will study the impact of neuronal Thy-1 for the maintenance of a quiescence state in astrocytes as well as for astrocyte activation, proliferation and apoptosis. Furthermore, we will identify the mechanism of Thy-1-mediated control of astrocyte activation, and investigate the regulation of neuronal Thy-1 expression. Finally, the impact of neuronal Thy-1 on other brain cells within the complex neural network like oligodendrocytes and microglial cells will be investigated.Our findings will substantially contribute to the understanding of the communication and interaction between astrocytes and neurons and might possibly provide new targets for the treatment of neurological diseases.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Johannes Hirrlinger, Ph.D.; Dr. Ute Krügel