Oncotarget

Research Papers: Neuroscience:

Role of Jnk1 in development of neural precursors revealed by iPSC modeling

Qian Zhang, Jian Mao, Xiaoxi Zhang, Haifeng Fu, Siyuan Xia, Zhinan Yin and Lin Liu _

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Oncotarget. 2016; 7:60919-60928. https://doi.org/10.18632/oncotarget.11377

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Abstract

Qian Zhang1, Jian Mao1, Xiaoxi Zhang1, Haifeng Fu1, Siyuan Xia1, Zhinan Yin1 and Lin Liu1

1 Department of Cell Biology and Genetics, State Key Laboratory of Medicinal Chemical Biology, 2011 Collaborative Innovation Center for Biotherapy, College of Life Sciences, Nankai University, Tianjin, China

Correspondence to:

Lin Liu, email:

Keywords: Jnk1, induced pluripotent stem cells (iPSCs), modeling disease, neural differentiation, neural precursors, Neuroscience

Received: May 23, 2016 Accepted: August 13, 2016 Published: August 18, 2016

Abstract

Jnk1-deficient mice manifest disrupted anterior commissure formation and loss of axonal and dendritic microtubule integrity. However, the mechanisms and the specific stages underlying the developmental defects remain to be elucidated. Here, we report the generation of Jnk1-deficient (Jnk1 KO) iPSCs from Jnk1 KO mouse tail-tip fibroblasts (TTFs) for modeling the neural disease development. The efficiency in the early induction of iPSCs was higher from Jnk1 KO fibroblasts than that of wild-type (WT) fibroblasts. These Jnk1 KO iPSCs exhibited pluripotent stem cell properties and had the ability of differentiation into general three embryonic germ layers in vitro and in vivo. However, Jnk1 KO iPSCs showed reduced capacity in neural differentiation in the spontaneous differentiation by embryoid body (EB) formation. Notably, by directed lineage differentiation, Jnk1 KO iPSCs specifically exhibited an impaired ability to differentiate into early stage neural precursors. Furthermore, the neuroepitheliums generated from Jnk1 KO iPSCs appeared smaller, indicative of neural stem cell developmental defects, as demonstrated by teratoma tests in vivo. These data suggest that Jnk1 deficiency inhibits the development of neural stem cells/precursors and provide insights to further understanding the complex pathogenic mechanisms of JNK1-related neural diseases.


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