The effect of P85 on neuronal proliferation and differentiation during development of mouse cerebral cortex

被引:7
作者
Cheng, Xinran [1 ]
Li, Kaikai [1 ]
Liu, MengMeng [1 ]
Xu, Mingrui [2 ]
Xu, Xinde [1 ,3 ]
Yan, Runchuan [1 ]
Forster, Eckart [4 ]
Zhao, Shanting [1 ]
机构
[1] Northwest A&F Univ, Coll Vet Med, Yangling 712100, Shaanxi, Peoples R China
[2] Northwest A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China
[3] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, State Key Lab Neurosci,Inst Neurosci, Key Lab Primate Neurobiol,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
[4] Ruhr Univ Bochum, Dept Neuroanat & Mol Brain Res, Univ Str 150, D-44801 Bochum, Germany
基金
中国国家自然科学基金;
关键词
P85; Cerebral cortex; Proliferation; Differentiation; Cell cycle; CELL-CYCLE PROGRESSION; NEURAL STEM-CELLS; PHOSPHOINOSITIDE; 3-KINASE; PROGENITOR CELLS; DEVELOPING NEOCORTEX; CORTICAL DEVELOPMENT; PI3K/AKT PATHWAY; KINASE; RAS; MALFORMATIONS;
D O I
10.1016/j.ydbio.2018.06.016
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Proliferation of neural stem cells and differentiation of newly generated cells are crucial steps during the development of mammalian neocortex, which are able to generate suitable number of neurons and glial cells to ensure normal formation of cortex. Any disturbance in these processes leads to structural and functional abnormalities of cerebral cortex, such as epilepsy or intellectual disability. Numerous molecules involved in the development of disorders of the nervous system have been discovered in the recent years. The PI3K/AICT signaling pathway has been shown to be widely involved in the corticogenesis. Recently we could show that overexpression of regulatory subunit P85 of PI3K disrupts neuronal migration. However, it remains unclear whether the regulatory subunit P85 plays a role in the proliferation of neural stem cells and differentiation of newly generated cells during mouse brain development. Here, by using in utero electroporation and immunohistochemistry, we show that overexpression of P85 inhibited proliferation of neural progenitor cells and neuronal differentiation. By using 5-bromo-2-deoxyuridine (BrdU) labeling, we reveal that overexpression of P85 extended the cell cycle duration, which may result in developmental retardation during mouse corticogenesis.
引用
收藏
页码:95 / 103
页数:9
相关论文
共 45 条
[1]   Early embryonic lethality in mice deficient in the p110β catalytic subunit of PI 3-kinase [J].
Bi, L ;
Okabe, I ;
Bernard, DJ ;
Nussbaum, RL .
MAMMALIAN GENOME, 2002, 13 (03) :169-172
[2]   Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process [J].
Caviness, VS ;
Goto, T ;
Tarui, T ;
Takahashi, T ;
Bhide, PG ;
Nowakowski, RS .
CEREBRAL CORTEX, 2003, 13 (06) :592-598
[3]   Direct positive regulation of PTEN by the p85 subunit of phosphatidylinositol 3-kinase [J].
Chagpar, Ryaz B. ;
Links, Philip H. ;
Pastor, M. Chris ;
Furber, Levi A. ;
Hawrysh, Andrea D. ;
Chamberlain, M. Dean ;
Anderson, Deborah H. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (12) :5471-5476
[4]   P85 regulates neuronal migration through affecting neuronal morphology during mouse corticogenesis [J].
Cheng, Xinran ;
Li, Kaikai ;
Liu, MengMeng ;
Hu, Xinde ;
Xu, Mingrui ;
Yan, Runchuan ;
Zhao, Shanting .
CELL AND TISSUE RESEARCH, 2018, 372 (01) :23-31
[5]   Regulation of cerebral cortical size by control of cell cycle exit in neural precursors [J].
Chenn, A ;
Walsh, CA .
SCIENCE, 2002, 297 (5580) :365-369
[6]   Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas [J].
Colman, H ;
Giannini, C ;
Huang, L ;
Gonzalez, J ;
Hess, K ;
Britner, J ;
Fuller, G ;
Langford, L ;
Pelloski, C ;
Aaron, J ;
Burger, P ;
Aldape, K .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 2006, 30 (05) :657-664
[7]   Evolving neurobiology of tuberous sclerosis complex [J].
Crino, Peter B. .
ACTA NEUROPATHOLOGICA, 2013, 125 (03) :317-332
[8]  
Cunningham JJ, 2001, CELL GROWTH DIFFER, V12, P387
[9]   Requirement for phosphatidylinositol-3 kinase activity during progression through S-phase and entry into mitosis [J].
Dangi, S ;
Cha, H ;
Shapiro, P .
CELLULAR SIGNALLING, 2003, 15 (07) :667-675
[10]   Phosphoinositide 3-kinase: Diverse roles in immune cell activation [J].
Deane, JA ;
Fruman, DA .
ANNUAL REVIEW OF IMMUNOLOGY, 2004, 22 :563-598