National Yang-Ming University -- Fu-Chin Liu Professor
Fu-Chin Liu Professor

Fu-Chin Liu Professor( Director of Institute of Neuroscience)
劉福清 Fu-Chin Liu Professor( Director of Institute of Neuroscience)
fuchin@ym.edu.tw
Tel : 886-2-2826-7216
Fax : 886-2-2820-0259

Ph.D., 1991, Massachusetts Institute of Technology
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Shangming Wang Xiaofang Wang Tzu Wei Wang Ching Ying Wu Xiaolin Wu

Shunyuan Li Yan Yi Lin
Hanjiang Jin Haojie Yao Xin An He Jialing Hu Yun Zhang Chuanci Zhang Xiao Ying Guo
Chiang Yun Chen Ke Zhen Chen Yi Quan Chen Huiying Chen Yinglan Feng Yujie Huang Dinghao Huang
Rui Qi Huang Wenlin Liao Jiawei Liu Xiuzhao Cai Guanming Lu Yihua Xie Jiawei Luo
Xianrou Hao Yi Xin Li (Doctor) Jingrui Lin Hao Yang
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Pierre Chambon Michael Wagner Hiroshi Takahashi
Toshihiko Aosaki Tetsuichiro Saito Yoshihide Hayashizaki
E. Bryan Crenshaw III Cary Lai Martin Gassmann
Josh Huang Ting-Fen Tsai Mingji Fan
Bo Wo Jian Huiyun Li Yuting Yan
Shuhua Lin
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image My laboratory is devoted to study neural development and plasticity of the basal ganglia circuits in the mammalian forebrain. The striatum is the major input component of the basal ganglia circuits. What makes the striatum an attractive and important system for neurobiological study is its involvement in processing multiple dimensions of neurological function ranging from movement, cognition and reinforcement to plasticity of learning and memory. The importance of the striatum is also reflected in a number of neurological disorders including Parkinson's disease, Huntington's disease, schizophrenia and mood disorders whose pathogeneses involve either degeneration or malfunction of the striatal system. The study of development and function of the striatum is thus fundamentally important not only to the understanding of integrative brain function, but also to the development of therapeutic approach to neurological diseases.

The long-term goal of our research is to elucidate how the infrastructure of the basal ganglia circuits is built to function and adapted to neural plastic changes in the brain. Our strategic approach is to identify the genetic programs underlying neurogenesis, neuronal specification and differentiation in the basal ganglia during development. To this end, we have identified striatum-enriched transcription regulators (Nolz-1, RAR/RXR, Isl-1, Six3, Foxp2) and receptor tyrosine kinase signaling molecules (NRG/ErbB4) that may be involved in neural development and plasticity of the basal ganglia system. We are currently analyzing different lines of gene knockout mice by cellular and molecular biology techniques. Our recent work of the gene regulation of Foxp2 in the developing striatum has led us to studying the primitive circuits engaged in speech and language. We are also approaching the neurobiological basis of schizophrenia, a complex neurodevelopmental disorder, based on our study of NRG/ErbB4 signaling in GABAergic interneurons of the forebrain.

We believe by identifying and characterizing the striatum-enriched transcriptional regulators and associated signaling molecules, we may gain insights into the neural mechanisms by which the basal ganglia circuits are built to function and adapted to environmental challenge. Our work also may be of clincal relevance, as identification of growth factor-associated molecules may provide information for treating neurodegenerative diseases.
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image Lu K-M, Evans, SM, Hirano S, Liu-F-C (2014) Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity. Proc Natl Acad Sci USA 111(1):E168-177.
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image Chang SL-Y, Chen S-Y, Huang H-H, Ko H-A, Liu P-T, Liu Y-C, Chen P-H, Liu F-C (2013) Ectopic Expression of Nolz-1 in Neural Progenitors Promotes Cell Cycle Exit/Premature Neuronal Differentiation Accompanying with Abnormal Apoptosis in the Developing Mouse Telencephalon. PLoS ONE 8(9): e74975. doi:10.1371/journal.pone.0074975.
image Chang L-Y, Liu Y-C, Chen S-Y, Huang T-H, Liu P-T, Liu F-C (2013) Identification of two evolutionarily conserved 5' cis-elements involved in regulating spatiotemporal expression of Nolz-1 during mouse embryogenesis. PLoS ONE 8:e54485.
image Chang L-Y,Yan Y-T, Shi Y-L, Liu Y-C, Takahashi H, Liu F-C (2011) Region- and cell type-selective expression of Nolz-1/zfp503 mRNA in the developing mouse hindbrain. Gene Expression Patterns 11:525-532.
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Chen C-M, Wang H-Y, You L-R, Shang R-L, Liu F-C (2010) Expression analysis of an evolutionary conserved metallophosphodiesterase gene, Mpped1, in the normal and β-catenin-deficient malformed dorsal telencephalon. Dev Dynamics 239:1797-1806.

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 Kaoru T, Liu F-C, Ishida M, Oishi T, Hayashi M, Kitagawa M, Shimoda K, Takahashi H (2010) Molecular characterization of the intercalated cell masses of the amygdala: implications for the relationship with the striatum. Neuroscience 166:220-230.

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Takahashi H, Takahashi K, Liu F-C (2009) FOXP genes, neural development, speech and language disorders In: Forkhead Transcription Factors: Vital Elements in Biology and Medicine, Section II, Chapter 9, pp1-13, Maiese K, editor, Landes Bioscience, Austin, Texas. (Invited book chapter)

image Chen Y-F, Kao C-H, Chen Y-T, Wang C-H, Wu C-Y, Tsai C-Y, Liu F-C, Yang C-W, Wei Y-H, Hsu M-T, Tsai S-F, Tsai T-F (2009) Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes & Development 23:1183-1194
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Sato T, Miura M, Yamada M, Yoshida T, Wood JD, Yazawa I, Masuda M, Suzuki T, Shin R-M, Yau H-J, Liu F-C, Shimohata T, Onodera O, Ross C A, Katsuki M, Takahashi H, Kano M, Aosaki T, Tsuji S (2009) Severe neurological phenotypes of Q129 DRPLA transgenic mice serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA mice. Human Molecular Genetics 18:723-736.

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Tsuchiya R, Takahashi K, Liu F-C, Takahashi H (2009) Aberrant axonal projections from mammillary bodies in Pax6 mutant mice: possible roles of Netrin-1 and Slit 2 in mammillary projections. J Neurosci Res 87:1620-1633.  

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Liao W-L, Tsai H-C, Wang H-F, Chang J, Lu K-M, Wu H-L, Lee Y-C, Tsai T-F, Takahashi T, Wagner M, Ghyselinck NB, Chambon P, Liu F-C (2008) Modular patterning of structure and function of the striatum by retinoid receptor signaling. Proc Natl Acad Sci 105: 6765-6770.

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Takahashi K, Liu F-C, Oishi T, Mori T, Higo N, Hayashi M, Takahashi H (2008) Expression of FOXP2 in the developing monkey forebrain: comparison with the expression of the genes FOXP1, PBX3 and MEIS2. J Comp Neurol 509:180-189.

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Takahashi K, Liu F-C, Hirokawa K, Takahashi H (2008) Expression of Foxp4 in the developing and adult rat forebrain. J Neuosci Res 86:3106-3116.

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Takahashi H, Liu F-C (2006) Genetic patterning of the mammalian telencephalon by morphogenetic molecules and transcription factors. Birth Defects Res C Embryo Today: Reviews 78:256-266. (Invited review)

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Wang H-F, Liu F-C (2005) Regulation of multiple dopamine signal transduction molecules by retinoids in the developing striatum. Neuroscience 134:97-105.

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Liao W-L, Liu F-C (2005) RAR( isoform-specific regulation of DARPP-32 gene expression: an ectopic expression study in the developing rat telencephalon. Eur J Neurosci 21: 3262-3268.

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Liao W-L, Tsai H-C, Wu C-Y, Liu F-C (2005) Differential expression of RARb isoforms in the mouse striatum during development: a gradient of RARb2 expression along the rostrocaudal axis. Dev Dynamics 233:584–594.

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Liao W-L, Wang H-F, Tsai H-C, Chambon P, Wagner M, Kakizuka A, Liu F-C (2005) Retinoid signaling competence and RARb-mediated gene regulation in the developing mammalian telencephalon. Dev Dynamics 232:887-900.  

image Chang C-W, Tsai C-W, Wang H-F, Tsai H-C, Chen H-Y, Tsai T-F, Takahashi H, Li H-Y, Fann M-J, Yang C-W, Hayashizaki Y, Saito T, Liu F-C (2004) Identification of a developmentally regulated striatum-enriched zinc-finger gene Nolz-1 in the mammalian brain. Proc Natl Acad Sci 101:2613-2618.
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Yau H-J, Wang H-F, Lai C, Liu F-C (2003) Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: preferential expression by interneurons tangentially migrating from the ganglionic eminences. Cerebral Cortex 13:252-264.

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Liu F-C (2003) Organotypic culture of developing striatum: Pharmacological induction of gene expression. In: Methods in Molecular Medicine, vol. 79: Drugs of Abuse: Neurological Reviews and Protocols, pp.405-412, Humana Press, Totowa, New Jersey . (Invited book chapter)  

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Takahashi K, Liu F-C, Hirokawa K, Takahashi H (2003) Expression of Foxp2, a gene involved in speech and language, in the developing and adult striatum. J Neuosci Res 73:61-72.

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Lee YC, Chien CL, Sun CN, Huang CL, Huang NK, Chiang MC, Lai HL, Lin YS, Chou SY, Wang CK, Tai MH, Liao WL, Lin TN, Liu FC, Chern Y (2003) Characterization of the rat A2A adenosine receptor gene: a 4.8-kb promoter-proximal DNA fragment confers selective expression in the central nervous system. Eur J Neurosci 7:1786-96.

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Wang H-F, Liu F-C (2001) Developmental restriction of the LIM homeodomain transcription factor Isl-1 expression to cholinergic neurons in the striatum. Neuroscience 103:999-1016.

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Liu F-C, Graybiel AM (1999) Neural development of the striatal dopamine system. In: The Development of Dopaminergic Neurons, (U. di Porzio, R. Pernas-Alonso, C. Perrone-Capano, eds), Landes Biosciences, Texas , pp.87-100.

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Liu F-C, Graybiel AM (1998) Phosphorylation of CREB in organotypic cultures of developing striatum: Kinetics of dopamine and calcium signal interactions. In: Advances in Pharmacology, vol. 42, Catecholamines: Bridging Basic Science with Clinical Medicine, (D.S. Goldstein, G. Eisenhofer, R. McCarty, eds), Academic Press, San Diego, California , pp.682-686.

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Liu F-C, Wu G-C, Hsieh S-T, Lai H-L, Wang H-F, Wang T-W, Chern Y (1998) Expression of adenylyl cyclase type VI in the central nervous system: Implication for a general coincidence detector in neurons, FEBS letters 436:92-98.  

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Liu F-C, Graybiel AM (1998) Region-dependent dynamics of cAMP response element-binding protein phosphorylation in the basal ganglia. Proc Natl Acad Sci USA 95: 4708-4713.  

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Liu F-C, Graybiel AM (1998) Activity-regulated phosphorylation of CREB in the developing striatum: Implications for patterning the neurochemical phenotypes of striatal compartments. Dev Neurosci 20:229-236.

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Liu F-C, Graybiel AM (1996) Protein phosphatases regulate CREB phosphorylation and Fos expression in the developing striatum: Evidence and a hypothesis. In: Advances in Behavioral Biology, vol. 47, The Basal Ganglia V,(C.Ohye, M. Kimura and J.S. McKenzie, eds), Plenum Press, New York , pp.97-103.  

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Liu F-C, Graybiel AM (1996) Spatiotemporal dynamics of CREB phosphorylation: Transient versus sustained phosphorylation in the developing striatum. Neuron 17:1133-1144.

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Liu F-C, Graybiel AM (1995) Dopamine-mediated signaling in organotypic striatal slice cultures. In: Molecular and Cellular Mechanisms of the Neostriatal Function, (M. A. Ariano and J. Surmeier, eds), R.G. Landes, Georgetown, Texas , pp.311-319.  

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Graybiel AM, Berretta B, Moratalla R, Liu F-C, Elibol B (1995) Effects of cocaine on signal transduction in striatal neurons. In: Neurobiology of Cocaine, (R. Hammer, ed), CRC Press, Boca Raton, Florida , pp.215-223.

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Liu F-C, Dunnett SB, Graybiel AM (1995) Embryonic striatal grafting: Progress and future directions for therapeutic approaches to neurodegenerative diseases of the basal ganglia. In: Age-related dopamine-dependent disorders, ( N. Segawa and Y. Nomura, eds), Karger, Basel , Monogr Neural Sci 14:225-234.

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Liu F-C, Takahashi H, McKay RDG, Graybiel AM (1995) Dopaminergic regulation of transcription factor expression in organotypic cultures of developing striatum. J Neurosci 15:2367-2384.  

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Liu F-C, Dunnett SB, Graybiel AM (1993) Intrastriatal grafts derived from fetal striatal primordia. IV. Host and donor neurons are not intermixed. Neuroscience 55:363-372.  

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Liu F-C, Dunnett SB, Graybiel AM (1992) Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia. J Neurosci 12:4281-4297.

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Liu F-C, Graybiel AM (1992) Transient calbindin-D28K-positive systems in the telencephalon: ganglionic eminence, developing striatum and cerebral cortex. J Neurosci 12:674-690.  

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Liu F-C, Graybiel AM (1992) Heterogeneous development of calbindin-D28K expression in the developing striatum. J Comp Neurol 320:304-322.

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Liu F-C, Dunnett SB, Robertson HA, Graybiel AM (1991) Intrastriatal grafts derived from fetal striatal primordia. III. Induction of modular patterns of Fos-like immunoreactivity by cocaine. Exp Brain Res 85:501-506.  

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Liu F-C, Graybiel AM, Dunnett SB, Baughman RW (1990) Intrastriatal grafts derived from fetal striatal primordia: II. Reconstitution of cholinergic and dopaminergic systems. J Comp Neurol 295:1-14.

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Graybiel AM, Liu F-C, Dunnett SB (1990) Cellular reaggregation in vivo: Modular patterns in intrastriatal grafts derived from fetal striatal primordia. Prog Brain Res 82:401-405.

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Graybiel, AM, Liu F-C, Dunnett SB (1989) Intrastriatal grafts derived from fetal striatal primordia. I. Phenotypy and modular organization. J Neurosci 9:3250-3271.



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