Lizheng Wang, University of Calgary
Article citation
Lizheng Wang, Qianqian Guo, Sandesh Acharya, Xiao Zheng, Vanessa Huynh, Brandon Whitmore, Askar Yimit, Mehr Malhotra, Siddharth Chatterji, Nicole Rosin, Elodie Labit, Colten Chipak, Kelsea Gorzo, Jordan Haidey, David A. Elliott, Tina Ram, Qingrun Zhang, Hedwich Kuipers, Grant Gordon, Jeff Biernaskie, Jiami Guo. Primary cilia signaling in astrocytes mediates development and regional-specific functional specification. Nature Neuroscience, 2024, 27 (9): 1708-1720.
Links
https://www.nature.com/articles/s41593-024-01726-z
https://drive.google.com/file/d/1_NWT1RLB4eEKYs-dVqreONw8RqBnjPnm/view?usp=drive_link
Uncovering the role of cilia in astrocyte development and function
Astrocytes are a type of cells that act as crucial regulators of nearly all aspects of the brain. Different types of astrocytes exist; however, little is known about how different subtypes of astrocytes are created during development to differentially support their local neural circuits. Lizheng Wang, working in the laboratory of Jiami Guo at the University of Calgary, has discovered that a structure called the primary cilia acts as a small signaling antennae to transmit local cues and drive the region-specific diversification of astrocytes within the developing brain, and plays important roles in brain development.
Discovered over 100 years ago, primary cilia are only beginning to be appreciated for their significance in the brain. Researchers have recently demonstrated that primary cilia of neurons are indispensable in regulating major neuronal development and functions, while the presence and function of cilia in astrocytes remained unexplored. This study shows that perturbation of astrocytic cilia leads to disruption of neuronal development and connections in the brain. Mice with primary ciliary deficient astrocytes show behavioral deficits in sensorimotor function, sociability, learning and memory.
These findings provide a new way to think about how primary ciliary deficiency exert profound impact on brain development and health, by enabling astrocytes to modulate communications and indirectly influence neuronal programs. These efforts to define the functional link between cilia and astrocytes are breaking new ground, uncovering a novel role for primary cilia in transmitting local cues that drive development of astrocytes within the developing brain. This work also opens future avenues for investigations into the cilia-mediated extracellular signals that configure astrocyte heterogeneity, and the potentially broad role of primary cilia in astrocyte signaling, metabolism, neuron-astrocyte communications, and inflammatory response underlying brain development, normal function and disease progression.
About Lizheng Wang
Dr. Lizheng Wang performed this work as a post-doctoral fellow in the laboratory of Dr. Jiami Guo at the University of Calgary.
Source of funding
This research was supported by The New York Stem Cell Foundation (NYSCF-R-N163 to J.G), the Canadian Institutes of Health Research (RN418797-438409 to J.G.), the National Science and Engineering Research Council (RGPIN-2019-04820 to J.G.). We thank the support from Harley N. Hotchkiss- Samuel Weiss Postdoctoral Fellowship (L.W.), Cumming School of Medicine Postdoctoral Scholarship (L.W.), and ACHRI STEP Postdoctoral Fellowship (L.W.).