Beta 1 integrin-mediated effects of tenascin-R domains EGFL and FN6-8 on neural stem/progenitor cell proliferation and differentiation in vitro.
Neural stem/progenitor cells (NSCs) have the capacity for self-renewal and differentiation into major classes of central nervous system cell types, such as neurons, astrocytes, and oligodendrocytes. The determination of fate of NSCs appears to be regulated by both intrinsic and extrinsic factors. Mounting evidence has shown that extracellular matrix molecules contribute to NSC proliferation and differentiation as extrinsic factors. Here we explore the effects of the epidermal growth factor-like (EGFL) and fibronectin type III homologous domains 6-8 (FN6-8) of the extracellular matrix molecule tenascin-R on NSC proliferation and differentiation. Our results show that domain FN6-8 inhibited NSC proliferation and promoted NSCs differentiation into astrocytes and less into oligodendrocytes or neurons. The EGFL domain did not affect NSC proliferation, but promoted NSC differentiation into neurons and reduced NSC differentiation into astrocytes and oligodendrocytes. Treatment of NSCs with beta 1 integrin function-blocking antibody resulted in attenuation of inhibition of the effect of FN6-8 on NSC proliferation. The influence of EGFL or FN6-8 on NSCs differentiation was inhibited by beta 1 integrin antibody application, implicating beta 1 integrin in proliferation and differentiation induced by EGFL and FN6-8 mediated triggering of NSCs.
Liao
Hong
H
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China. Electronic address: liaohong56@hotmail.com.
Huang
Wenhui
W
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China; Zentrum für Molekulare Neurobiologie, University of Hamburg, D-20251 Hamburg, Germany.
Schachner
Melitta
M
Zentrum für Molekulare Neurobiologie, University of Hamburg, D-20251 Hamburg, Germany; Keck Centre for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854.
Guan
Yue
Y
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China.
Guo
Jingjing
J
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China.
Yan
Jun
J
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China.
Qin
Jing
J
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China.
Bai
Xianshu
X
Neurobiology Laboratory, New Drug Screening Centre, China Pharmaceutical University, Nanjing 210038, China.
Zhang
Luyong
L
Jiangsu Center for Pharmacodynamic Research and Evaluation, China Pharmaceutical University, Nanjing 210038, China. Electronic address: lyzhang@cpu.edu.cn.
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004815:Epidermal Growth Factor; D005353:Fibronectins; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D019063:Tenascin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D005353:Fibronectins; D019012:Integrin beta1; D011994:Recombinant Proteins; D019063:Tenascin; C074638:tenascin R; D004815:Epidermal Growth Factor