Unveiling the Hidden Architectures of the Brain ECM

2022 Seed Grant
Sungjin Park, Ph.D.
University of Utah

The extracellular matrix (ECM) maintains cellular integrity, provides a nurturing niche, regulates signaling activity, and transduces mechanical force. In the brain, ECM plays a critical role in a variety of functions, including providing niches for neurogenesis and synaptogenesis, maintaining the integrity of the blood-brain barrier, regulating the clearance of toxic molecules from the extracellular space, forming glial scars after injuries, and regulating cancer cell proliferation and invasion. Notably, brain ECM directly regulates neuronal plasticity and behavior. However, the structure and function of the brain ECM are poorly understood due to its innate flexibility and the lack of longitudinal tools that monitor the dynamic changes in brain ECM architectures. Noting that the brain ECM is structured by link proteins that connect the sugar backbone and proteoglycans, Dr. Park’s laboratory targeted a link protein and established an assay system that reveals brain ECM architectures (we named H-Link). Surprisingly, H-Link reveals novel populations of brain ECM architectures that are not recognized by conventional tools. In particular, H-Link shows that even excitatory neurons are surrounded by a structured architecture (perineuronal net: PNN). With the tool they developed, Dr. Park’s lab will characterize the diverse populations of brain ECM architectures and their dynamic changes during development. They expect that the proposed study will provide significant conceptual and technical innovations to our understanding of the structure and function of the brain ECM that will be of broad relevance to various brain functions/dysfunctions.

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