Nature. The time Songhai/Sihang team revealed the anchoring of the central body to regulate the characteristics of the neuroprecursor cells and the formation of the cerebral cortex.

The brain is the highest center of the nervous system, which controls such high-level neural activities as perception, movement, language, thinking and cognition.it is very important to study the development and regulation mechanism of brain nervous system, to strengthen the cognition of nervous system, and to diagnose and treat nervous system related diseases.radial glial cells are the key neural precursor cells in mammalian brain development. They divide and produce almost all neurons and glial cells in the cerebral cortex.during brain development, the behavior of radial glial cells is highly ordered [1].as the main microtubule tissue center of animal cells, centrosome regulates the process of cell cycle and plays an important regulatory role in the development of brain nervous system [2].centrosomes are usually located in the cytoplasm near the nucleus. However, in radial glial cells, the centrosome is located on the apical cell membrane far away from the nucleus, that is, on the surface of the ventricular cavity [3,4].this unique subcellular feature has been found for decades, but its cause and function have been puzzling.on March 25, 2020, Professor Shi Songhai of IDG McGovern Institute of brain sciences and School of life sciences of Tsinghua University and research group of Shi Hang, researcher of advanced innovation center of structural biology, published online the title "centrosome anchoring regulations progenitor properties and cortical" in nature The research paper of "formation" (the anchoring of centrosome regulates the characteristics of neural precursor cells and the formation of cerebral cortex), which for the first time reveals the new mechanism that centrosome regulates the mechanical properties and division ability of neural precursor cells in mammalian cerebral cortex, and then affects the size and folding of cerebral cortex.in this paper, the researchers firstly observed the brain tissue of embryonic mice by using the continuous ultrathin section technology based on transmission electron microscope imaging, and observed for the first time that the centrosome in radial glial cells was anchored to the apical cell membrane through the distal appendages attached to the maternal centriole (Fig. 1).in order to explore the molecular regulatory mechanism and physiological function of centrosome localization, the researchers specifically removed cep83, an important component of the distal appendage in radial glial cells of the cerebral cortex, so that no distal attachment was formed on the maternal centriole, resulting in a slight dislocation between the centrosome and the apical membrane, thus preventing the anchoring and connection between the centrosome and the cell membrane (Fig 1）。[Fig. 1] the centrosome is anchored to the apical membrane through the distal appendage.interestingly, the volume of cerebral cortex increased significantly in adult mice after specific destruction of centrosome anchoring in radial glial cells, and abnormal folding was common in the dorsal raphe area of the cortex (Fig. 2a).further studies have found that this abnormal phenotype results from the excessive proliferation of radial glial cells in the early stage of neurogenesis and the increase of intermediate precursor cells after neurogenesis (Fig. 2b).[figure 2] cep83 specific knockout resulted in increased cortical volume and abnormal folding.How are neurogenesis abnormalities caused? Further study found that the dislocation of centrosome less than 1 μ m destroyed the unique circular microtubule structure on the apical membrane, resulting in the stretching and hardening of the apical membrane.changes in the physical properties of the apical membrane caused the Yap protein (yes associated) associated with the mechanical sensitive signal pathway in radial glial cells The excessive activation of protein leads to the excessive expansion of pre radial glial cells and the increase of intermediate precursor cells. Finally, the number of neurons in cerebral cortex increases significantly, and the volume of cortex expands, which leads to abnormal folding.consistent with this, the simultaneous knockout of Yap can restore the cortical volume to the normal level without folding (Fig. 3). [figure 3] centrosome anchoring regulates the mechanical properties of the apical membrane of radial glial cells and Yap signals, resulting in an increase in the number of nerve cells and the expansion of cortical volume. this study solved a long-standing puzzle about the cause and role of centrosome in radial glial cells, and provided a new perspective for the study of neural precursor cell behavior and cortical development regulation. in addition, previous studies have shown that centrosome protein related mutations are generally closely related to microcephaly. However, this study found that centrosome protein mutations lead to macrocephaly, and for the first time revealed its mechanism. more importantly, human cep83 biallelic mutation can lead to ventricular volume enlargement, mental retardation and renal wasting disease in children. This study provides important clues for revealing the morphological and intellectual abnormalities of human cortex. Wei Shao of Cornell Medical College and Yang Jiajun, doctoral student of School of life sciences, Tsinghua University, are the co first authors of this paper. he Ming, PhD student, School of life, Peking University; Xiangyu, Ph.D., School of life, Tsinghua University; Zhao Hui Yang, Cornell Medical School; Alexandra L. Joyner, Kathryn v. Anderson, Meng Fu Bryan Tsou, Choong Heon Lee and Jiang Yang Zhang, School of medicine, New York University participated in the study. Professor Shi Songhai and researcher Shi Hang of Tsinghua University are the co authors of this paper. [1] Gao, P., Postiglione PIA, M., Krieger, t.g., Hernandez, L., T., Wang, C., Han, Z., Streicher, C., C., papusheva, e., insulara, R., Chugh, K., Kodish, O., Huang, K., K., K., Kodish, O., Huang, K., K., Simons, B.D., Luo, L., hippenmeyer, S., and Shi, S. - H. (2014) 2014) deterministic producer behavior and united production of nerve production of nerve production of nerve production of nerve, S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., S., ons in the Neocortex. Cell 159:775-788.【2】 Insolera, R., Bazzi, H., W. Shao, Anderson, K.V., and Shi, S.-H. (2014) Cortical Neurogenesis in the Absence of Centrioles. Nat. Neurosci. 17:1528-1535【3】 Wang, X., Tsai, J.-W., Imai, J.H., Lin, W.-N., Valle, R.B., and Shi, S.-H. (2009) Asymmetric Centrosome Inheritance Maintains Neural Progenitors in the Neocortex. Nature 461: 947-955.【4】 Bultje, R.S., Castaneda-Castellanos, D.R., Jan, L.Y., Jan, Y.N., Kriegstein, A.R., and Shi, S.-H. (2009) Mammalian Par3 Regulates Progenitor Cell Asymmetric Division via Notch Signaling in the Developing Neocortex. Neuron 63: 189-202