Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through
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Cellular and Molecular Life Sciences
RESEARCH ARTICLE
Protein tyrosine phosphatase receptor type O (Ptpro) regulates cerebellar formation during zebrafish development through modulating Fgf signaling Wei-Hao Liao · Chia-Hsiung Cheng · Kuo-Sheng Hung · Wen-Ta Chiu · Gen-Der Chen · Pung-Pung Hwang · Sheng-Ping L. Hwang · Yung-Shu Kuan · Chang-Jen Huang
Received: 6 August 2012 / Revised: 13 December 2012 / Accepted: 3 January 2013 / Published online: 30 January 2013 © The Author(s) 2013. This article is published with open access at Springerlink.com
Abstract Protein activities controlled by receptor protein tyrosine phosphatases (RPTPs) play comparably important roles in transducing cell surface signals into the cytoplasm by protein tyrosine kinases. Previous studies showed that several RPTPs are involved in neuronal generation, migration, and axon guidance in Drosophila, and the vertebrate hippocampus, retina, and developing limbs. However, whether the protein tyrosine phosphatase type O (ptpro), one kind of RPTP, participates in regulating vertebrate brain development is largely unknown. We isolated the zebrafish ptpro Electronic supplementary material The online version of this article (doi:10.1007/s00018-013-1259-7) contains supplementary material, which is available to authorized users. W.-H. Liao · C.-J. Huang Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 104, Taiwan W.-H. Liao · C.-H. Cheng · G.-D. Chen · Y.-S. Kuan · C.-J. Huang (*) Institute of Biological Chemistry, Academia Sinica, 128 Academia Rd, Sec 2, Taipei 115, Taiwan e-mail: [email protected] K.-S. Hung · W.-T. Chiu Department of Neurosurgery, Taipei Medical University-Wan Fang Hospital, Taipei 116, Taiwan P.-P. Hwang · S.-P. L. Hwang Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan Y.-S. Kuan (*) · C.-J. Huang Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan e-mail: [email protected] Y.-S. Kuan Neuroscience Program, Academia Sinica, Taipei 115, Taiwan
gene and found that its transcripts are primarily expressed in the embryonic and adult central nervous system. Depletion of zebrafish embryonic Ptpro by antisense morpholino oligonucleotide knockdown resulted in prominent defects in the forebrain and cerebellum, and the injected larvae died on the 4th day post-fertilization (dpf). We further investigated the function of ptpro in cerebellar development and found that the expression of ephrin-A5b (efnA5b), a Fgf signaling induced cerebellum patterning factor, was decreased while the expression of dusp6, a negative-feedback gene of Fgf signaling in the midbrain-hindbrain boundary region, was notably induced in ptpro morphants. Further analyses demonstrated that cerebellar defects of ptpro morphants were partially rescued by inhibiting Fgf signaling. Moreover, Ptpro physically interacted with the Fgf receptor 1a (Fgfr1a) and dephosphorylated Fgfr1a in a dose-dependant manner. Therefore, our findings demonstrate that Ptpro activity is required
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