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Int J Clin Exp Pathol 2012;5(7):634-641

Original Article
Sema3F downregulates p53 expression leading to axonal growth cone collapse in
primary hippocampal neurons

Guanglu Yang, Xiang Qu, Junmei Zhang, Weidong Zhao, Hua Wang

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang 110004, China; Department of Pediatrics, the Affiliated
Hospital of Inner Mongolia Medical University, Huhhot 010050, China; Department of Developmental Biology, China Medical University,
Shenyang 110001, China

Received May 25, 2012; Accepted July 26, 2012; Epub September 5, 2012; Published September 15, 2012

Abstract: Hippocampal nerve growth is regulated by the coordinated action of numerous external stimuli, including positively acting
neurotrophin-derived growth cues and restrictive semaphorin cues, however the underlying cellular mechanisms remain largely unclear. We
examined the potential cellular mechanism of Semaphorin3F (Sema3F) in cultured primary hippocampal neurons. We show that Sema3F can
down-regulate p53 expression in primary hippocampal neurons, thereby contributing to growth cone collapse. Sema3F suppressed
p53-induced pathways, which we show to be required to maintain growth cone structure. Sema3F-induced growth cone collapse was partially
reversed by overexpression of p53, which promoted growth cone extension. Inhibition of p53 function by inhibitor, siRNAs, induced axonal
growth cone collapse, whereas p53 over-expression led to larger growth cones in cultured primary hippocampal neurons.These data reveal a
novel mechanism by which Sema3F can induce hippocampal neuron growth cone collapse and provide evidence for an intracellular
mechanism for cross talk between positive and negative axon growth cues. (IJCEP1205011)

Keywords: Sema3F, p53, hippocampal neurons, collapse, transfection, growth cone

Address all correspondence to:
Hua Wang, MD
Department of Pediatrics
Shengjing Hospital of China Medical University
No. 36 Sanhao Street
Shenyang 110004, China.
Tel: 0086-13940110963; Fax: 0086-024-23892617
E-mail: wangh1@sj-hospital.org