大阪大学 蛋白質研究所 蛋白質高次機能学研究部門 分子発生学研究室


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Inrroduction of Furukawa lab
  • Furukawa lab research
  • Profile of Dr.Furukawa


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  • Prof. Takahisa Furukawa
    Laboratory for Molecular and Developmental Biology
    Institute for Protein Research
    Osaka University
    3-2 Yamadaoka
    Suita, Osaka, 565-0871
    Japan

  • +81-6-6879-8631

    +81-6-6879-8633

    takahisa.furukawa(at)
    protein.osaka-u.ac.jp

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Furukawa lab reseach

More than a hundred billion of neurons reside in the human brain. These enormous numbers of neurons are variable in terms of their morphologies, gene expressions, neurotransmitter types and functions. How is the information to control both precise identities of these neurons and formation of complicated neural networks programmed on our DNA? How does each neuron and glia choose their cell fate from common progenitors? How does each neuron precisely recognize other neurons and form correct synapses? How does each neural circuit realize physiological function and behavior? Finally, how is malformation or dysfunction of these steps related to our diseases? Our lab is challenging these problems by using the retina as a model system to explore the CNS. Our main technical approaches are molecular biology, histology, physiology, and mouse molecular genetics using KO/transgenic mice including BAC transgenic and conditional KO mice.



Research themes

I. Molecular mechanism of synapse formation in the retina
II. Mechanisms of cell fate determination of the vertebrate retina
III. Elucidation of functional roles of microRNAs (miRNAs) in CNS development
IV. Mechanisms of cilia formation using molecular genetics of zebrafish
V. Generation of KO/transgenic mice and analysis of visual function of genetically engineered mice


I. Molecular mechanism of synapse formation in the retina

Ultrastructural images of ribbon synapses in the wild-type (left) and pikachurin KO (right) mouse retinas.
In the wild-type retina, a normal rod synaptic terminus contains an invaginating bipolar terminus, in contrast, the pikachurin KO retina lacks bipolar terminus.




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II. Mechanisms of cell fate determination of the vertebrate retina

We are studying cell fate determination of retinal photoreceptors as a model system of the vertebrate CNS. The photoreceptor-specific conditional KO mouse retina displays a dramatic cell fate conversion from photoreceptor precursors (PR) to amacrine-like neurons (A).









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III. Elucidation of functional roles of microRNAs (miRNAs) in CNS development

Rncr3 encodes microRNA-124a-1 (miR-124a-1). The Rncr3 KO mouse shows aberrant sprouting of mossy fibers. The mossy fiber terminals were visualized by Timm staining with Nissl counterstaining at P10. (Sanuki et al., 2011, Nat. Neurosci)











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IV. Mechanisms of cilia formation using molecular genetics of zebrafish


Cilia of the inner ear in zebrafish (green).
Kinocilia of inner ear hair cells in zebrafish embryos were stained with the anti-acetylated alpha tubulin antibody (green). Actin-based stereociliary bundles of hair cells were stained with phalloidine (red).












A cilia mutant of zebrafish.
Mutant larvae with the defective cilia exhibit characteristic abnormalities such as curly body axis and kidney cysts.






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V. Generation of KO/transgenic mice and analysis of visual function of genetically engineered mice

A movie of microinjection into pronucleus of a mouse fertilized egg for generating transgenic mice (Please click it!).










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Graduate school/postdoc from abroad

We welcome graduate school students and postdocs from outside Japan to our lab. I am an adjunct professor of Kyoto University Graduate School of Medicine and Osaka City University Graduate School of Medicine. An applicant can apply for either or both of these graduate schools. An applicant needs to find a fellowship. We are happy to support applicants to apply for a JSPS/MEXT fellowship or other available fellowships.

For postdoc applicants;
JSPS Postdoctoral Fellowship for Foreign Researchers
URL: http://www.jsps.go.jp/j-fellow/main.htm

For graduate school applicants;
Japanese Government (MEXT) Scholarship
Honors Scholarships for Privately Financed Foreign Students
URL: http://www.mext.go.jp/english/abroad/foreigners/04061801.htm

We also welcome summer students or short-term visiting scientists from abroad.
If interested, please contact Dr. Furukawa by e-mail.

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Profile of Dr.Furukawa


Name Takahisa Furukawa
Current affiliation Osaka University,
Institute for Protein Research,
Laboratory for Molecular and Developmental Biology
Specialties Developmental Neurobiology, Biology & Medicine
Academic degree M. D. & Ph. D.



Research history
1988 M. D. in Medical School, Osaka University
1992 Ph. D. in Medical Chemistry, Kyoto University Faculty of Medicine
First isolation of a major signal transducer of Notch signal pathway. Molecular clarification of Notch signal transduction mechanism from membrane receptor to transcription in cell nucleus.
1995 Postdoctoral Fellow, Department of Genetics & Howard Hughes Medical Institute, Harvard Medical School
Isolation of a novel key transcription factor, Crx, which governs the terminal differentiation of photoreceptor cells by regulating the transcription of various photoreceptor specific genes.  Crx is the molecule that many researchers in this filed had been trying to identify for many years.  Important finding that mutations of the human Crx gene can cause three types of retinal degeneration diseases.  
Identification and analysis of the functionally one of the most upstream gene, rax, in eye development.
Elucidation of the mechanisms for dorsal-ventral axis formation in the eye
development.
1999 Assistant Professor of Center for Developmental Biology and Biochemistry at UTSW Medical Center at Dallas
Molecular description of cell fate decision of retinal glia cells by rax.
Discovery of the molecular mechanism for the terminal differentiation of retinal photoreceptor cells.
2001 Lab Head of Department of Developmental Biology, Osaka Bioscience Institute
2003 Adjunct Professor of Kyoto University Graduate School of Medicine
2004 Adjunct Professor of Osaka City University Graduate School of Medicine
We reveled that transcription factor Otx2 is necessary and sufficient for cell fate determination of retinal photoreceptor cells by using mouse molecular genetics. Our findings demonstrated that Otx2 could functions as a master gene in the cell fate determination of photoreceptor cells. Clarification that Otx2 is a direct upstream activator of Crx transcription, indicatinged that the transcription factor network has a critical role in the development of central nervous system neurons. Finding that the cell polarity of photoreceptor cells is essential for the normal formation of total retinal layer structure. Establishment of cell type-specific gene targeting system in the retina. Isolation and functional analysis of a novel extracelluar matrix protein, pikachurin. We revealed that pikachurin is a ligand for Dystroglycan and essential for synapse formation between photoreceptor and bipolar neurons.
2012 Professor of Insitute for Protein Research, Osaka University




Awards
2005 Pfizer Ophthalmics Award Japan
2006 Baelz prize
2007 Japan Society for the Promotion of Science Prize



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