Development and fucntion of neural circuits (retina and retinotectal system)
    Cell-cell Interaction (cell adhesion moleucles) and extracellular matrix
    Cutting-edge tool development using cell-cell interaction molecules



    In 2002, we obtained chicken cDNAs encoding Sdk1 and Sdk2, homologs of the fly sidekick (sdk) gene (Yamagata et al., 2002). Vertebrates have Sdk1 and Sdk2. Sdk is also present in C. elegans. The predicted vertebrate, insect, and nematode SDK proteins are similar in size and share an identical domain structure. From N to C terminus, each SDK protein consists of a signal sequence, 6 immunoglobulin C2 motifs, 13 fibronectin type III motifs, a single transmembrane domain, and an ~200aa cytoplasmic domain. A C-terminal GFSSFV (=PDZ-binding motif) is conserved in all SDKs, and is involved in synaptic localization.

    We showed that Sdk1 and Sdk2 mediate homophilic adhesion in vitro and direct lamina-specific neuronal connections in vivo. Our subsequent results suggested the existence of an Immunoglobulin superfamily code for laminar specificity and synaptic function in retina and, by implication, in other areas of the CNS

     (see Yamagata M (2020) Structure and functions of Sidekicks https://doi.org/10.3389/fnmol.2020.00139).


    Lamina-specific neuronal connections

    In many parts of the CNS of vertebrates and invertebrates, a prominent wiring diagram of neuronal circuits is laminar specificity.


    Synaptic adhesion molecule

    Synaptic adhesion molecules are a panoply of cell adhesion molecules involved in the development and maintenance of synapses.

    These molecules are localized transiently or permanently at mature and/or developing synapses, and in many cases, they are enriched in the synaptic membranes.

     Attribution Non-Commercial; No Derivatives:This image is licensed under a Creative Commons Attribution, Non-Commercial, No Derivatives License


    Connectomics (English translation)

    Connectomics reveals complex neural circuits in which neurons are connected via synapses. Synapses are actually derivatives of cell-cell contacts.


    Nanobody (English translation)

    Nanobodies are "Programmable proteins" useful for localizing specific molecules. 

    SynBio Special Issue

    " Programmable proteins in synthetic biology"


    Genome editing (CRISPR)
    Read this article "Creating Novel Cell Lines By Genome Editing"
    eCHIKIN (electroporation- and CRISPR-mediated Homology-Instructed Knock-IN)
    scRNAseq (English translation)
    A cell atlas of the chick retina based on single cell transcriptomics
    Frontiers Research Topic
    "Understanding Neural Circuits Using Single-Cell Technologies" 
    Chick cell atlas
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    Research Articles


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    Research topics

    1999年に表紙を飾りました。その他、Priciniples of Neural Science (Kandelら)でも紹介されています。

    Lamina-specific neuronal connections

    A prominent feature of the tissue architecture of the vertebrate central nervous system, including the mammalian cerebral cortex and hippocampus, is its laminated structure. In this structure, neurons, external inputs, and external outputs are functionally arranged and synaptically connected to build neural networks and information processing systems.
    To address the question of how the detailed circuits that connect neurons and external inputs in the layered structure are assembled, we have studied the synaptic connections of RGC axons (optic nerves) to the optic tectum and RGCs in the retina using chicks as a model.
    There are subsets of RGCs, each of which establishes synaptic connections at different retinorecipient tectal layers. To find the differences between these RGC subsets, we used a molecular biological approach in which cDNAs were amplified from a single cell by PCR (single cell PCR) and compared between different cells. As a result, they identified a number of molecular markers (transcription factors, neuropeptides, adhesion molecules, etc.) that are useful for analyzing neural connections, and also found the Sidekick molecules, which are explained in the next section.
    More recently, single-cell RNA sequencing analysis performed on chick retinas has been useful for studying cell surface molecules that are differentially expressed in different cell types.


    Yamagata M. (2017) Lamina-specific neuronal connections. In: Reference module in Neuroscience and Biobehavioral Psychology (Elsevier).



    Yamagata M. (2009) Lamina-Specific Neuronal Connections. In: Encyclopedia of Neuroscience (Squire LR (ed.)) Oxford, England, Academic Press. Volume. 5, pp. 299-305.


    Sanes JR, Yamagata M. (2009) Annu Rev Cell Dev Biol. 25:161-195. Many paths to synaptic specificity.



    Sanes, J. R. and Yamagata, M. (1999). Curr. Op. Neurobiol. 9, 79-87.

    Formation of lamina-specific synaptic connections


    (⬅ Cover)


    Yamagata, M., Weiner, J. A., Dulac, C., Roth, K. A., and Sanes, J. R. (2006). Mol Cell Neurosci. 33:296-310. Labeled lines in the retinotectal system: Markers for retinorecipient sublaminae and the retinal ganglion cell subsets that innervate them.


    Yamagata, M., Sanes, J. R. (2005) J. Neurosci. 25:8457– 8467. Versican in the developing brain: Lamina-specific expression in interneuronal subsets and role in presynaptic maturation.


    Yamagata, M. and Sanes, J. R. (1995). Development. 121, 3763-3776.

    Target-independent diversification and target specific projections of chemically coded retinal ganglion cell.


    Yamagata, M. and Sanes, J. R. (1995). Development 121: 189-200.

    Lamina-specific outgrowth and arborization of retinal axons in chick optic tectum.

    Synaptic adhesion molecules and neural circuit formation

    Yamagata M. (2020). Structure and functions of Sidekicks.

    Front. Mol. Neurosci., https://doi.org/10.3389/fnmol.2020.00139


    Yamagata M. (2009) Synaptic adhesion molecule. In: Encyclopedia of Neuroscience (Binder MD, Hirokawa N, Windhorst U (eds.)) Springer-Verlag, Berlin, Germany. pp. 3945-3948. 



    Yamagata, M., Sanes, J. R., and Weiner, J. A. (2003). Curr. Op. Cell Biol. 15, 623-631.  Synaptic adhesion molecules.



    Yamagata, M., and Sanes, J. R. (2019). Front. Mol. Neurosci. 11, 485. Expression and roles of the immunoglobulin superfamily recognition molecule sidekick1 in mouse retina.

    doi: 10.3389/fnmol.2018.00485


    Yamagata M, Duan X, Sanes JR. (2018) Cadherins Interact With Synaptic Organizers to Promote Synaptic Differentiation. Front Mol Neurosci. 11:142. doi: 10.3389/fnmol.2018.00142.


    Goodman KM*, Yamagata M*, Jin X, Mannepalli S, Katsamba PS, Ahlsén G, Sergeeva AP, Honig B,Sanes JR, Shapiro L. (*equal contribution) (2016) eLife. 2016 Sep 19;5. pii: e19058. doi: 10.7554/eLife.19058.

    Molecular basis of sidekick-mediated cell-cell adhesion and specificity.

    Molecular interaction of Sdk molecules ➡



    Krishnaswamy A*, Yamagata M*, Duan X, Hong YK, Sanes JR. (*equal contribution) (2015) Nature. 524:466-470.

    Sidekick 2 directs formation of a retinal circuit that detects differential motion.


    Yamagata M and Sanes JR (2012). J Neurosci. 32:14402-14414. Expanding the Ig superfamily code for laminar specificity in retina: expression and role of contactins.


    Yamagata M, Sanes JR. (2010) J. Neurosci.. 30:3579-3588. Synaptic localization and function of Sidekick recognition molecules require MAGI scaffolding proteins.


    Yamagata M, Sanes JR. (2008) Nature. 451:465-469. Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina.

    Yamagata, M., Weiner, J. A., Sanes, J. R. (2002). Cell 110: 649-660.

    Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina.


    Yamagata, M., Herman, J.-P., and Sanes, J. R. (1995). J. Neurosci. 15, 4556-4571.

    Lamina-specific expression of adhesion molecules in developing chick optic tectum.



    Yamagata M, Sanes JR. (2018).Reporter-nanobody fusions (RANbodies) as versatile, small, sensitive immunohistochemical reagents. Proc Natl Acad Sci U S A. 115:2126-2131. DOI: 10.1073/pnas.1722491115.


    Maximilian Joesch , David Mankus , Masahito Yamagata , Ali Shahbazi , Richard Schalek, Adi Suissa-Peleg, Markus Meister, Jeff W. Lichtman, Walter J. Scheirer, Joshua R. Sanes (2016) eLife, oi.org/10.7554/eLife.15015 Reconstruction of genetically identified neurons imaged by serial-section electron microscopy.


    Martell JD, Yamagata M, Deerinck TJ, Phan S, Kwa CG, Ellisman MH, Sanes JR, Ting AY. (2016) Nature Biotechnol. 34: 774-780. A split horseradish peroxidase for the detection of intercellular protein-protein interactions and sensitive visualization of synapses.

    split HRP


    Yamagata M and Sanes JR (2012) Transgenic strategy for identifying synaptic connections in mice by fluorescence complementation (GRASP). Front. Mol. Neurosci. 5:18. doi: 10.3389/fnmol.2012.00018


    Yamagata, M. (2022)
    Towards Tabula Gallus
    Int. J. Mol. Sci. 23, 613.



    Yamagata, M., Sanes, J. R. (2021)
    CRISPR-mediated Labeling of Cells in Chick Embryos Based on Selectively Expressed Genes. Bio-protocol 11, e4105


    Yamagata, M., Yan, W., Sanes, J. R. (2021)
    A cell atlas of the chick retina based on single cell transcriptomics. eLife


    Farhi, S. L., Parot, V. J., Grama, A., Yamagata, M., Abdelfattah, A. S., Adam, Y., Lou, S., Kim, J. J., Campbell, R. E., Cox, D. D., et al. (2019). Wide-Area All-Optical Neurophysiology in Acute Brain Slices. J. Neurosci. 39, 4889–4908


    Skocek O, Nobauer T, Weilguny L, Traub FM, Xia C, Molodtsov M, Aharoni D, Golshani P, Grama AS , Yamagata M, Cox D, and Vaziri A. (2018) High-speed volumetric imaging of neuronal activity in freely moving rodent. Nature Methods, 15: 429-432.


    Duan, X., Krishnaswamy, A., Laboulaye, M. A., Liu, J., Peng, Y.-R., Yamagata, M., Toma, K., and Sanes, J. R. (2018). Cadherin combinations recruit dendrites of distinct retinal neurons to a shared interneuronal scaffold. Neuron 99, 1145-1154.e6.


    Basu, R., Duan, X., Taylor, M. R., Martin, E. A., Muralidhar, S., Wang, Y., Gangi-Wellman, L., Das, S. C., Yamagata, M., West, P. J., Sanes, J. R. and Williams, M. E. (2017). Heterophilic type II cadherins are required for high-magnitude synaptic potentiation in the hippocampus. Neuron 96, 160–176.


    Cohen, O., Vald, L., Yamagata, M., Sanes, J. R. and Klar, A. (2017). Roles of DSCAM in axonal decussation and fasciculation of chick spinal interneurons. Int. J. Dev. Biol.61, 235–244.


    Rousso DL, Qiao M, Kagan RD, Yamagata M, Palmiter RD, Sanes JR.(2016) Cell Rep. 15:1930-1944. Two Pairs of ON and OFF Retinal Ganglion Cells Are Defined by Intersectional Patterns of Transcription Factor Expression.


    Poliak S, Norovich AL, Yamagata M, Sanes JR, Jessell TM.(2016) Cell 164:512-525.

    Muscle-type Identity of Proprioceptors Specified by Spatially Restricted Signals from Limb Mesenchyme.


    Kay JN, De la Huerta I, Kim IJ, Zhang Y, Yamagata M, Chu MW, Meister M, Sanes JR.(2011). J Neurosci. 31:7753-7762.Retinal ganglion cells with distinct directional preferences differ in molecular identity, structure, and central projections.


    Kim IJ, Zhang Y, Yamagata M, Meister M, Sanes JR. (2008) Nature.;452:478-482. Molecular identification of a retinal cell type that responds to upward motion.


    Yuasa, J., Hirano. S., Yamagata, M., and Noda, M. (1996). Nature 832, 632-635. Visual projection map specified by topographic expression of transcription factors in the retina.


    Yamagata, M., Jaye, D. L. and Sanes, J. R. (1994). Dev. Biol. 166: 355-359.

    Gene transfer to avian cells and tissues with a recombinant adenovirus.


    Yamagata, M. and Kimata, K. (1994). J. Cell Sci. 107: 2581-2590.

    Repression of malignant cell-substratum adhesive phenotype by inhibiting the production of anti-adhesive proteoglycan, PG-M/versican.


    Yamagata, M., Merlie, J.P., and Sanes, J.R. (1994). Gene 139: 223-228.

    Interspecific comparisons reveal conserved features of the Drosophila Toll protein.


    Yamagata, M., Saga, S., Kato, M., Bernfield, M., and Kimata, K. (1993). J. Cell Sci. 106: 55-65.

    Selective distributions of proteoglycans and their ligands in pericellular matrix of cultured fibroblasts --- Implications for their roles in cell-substratum adhesion.


    Yamagata, M., Shinomura, T. and Kimata, K. (1993). Anat. Embryol. 176: 433-444.

    Tissue variation of two large chondroitin sulfate proteoglycans (PG-M/versican and PG-H/aggrecan) in chick embryos.


    Yamagata, M., Yamada, K.M., Yamada, S., Shinomura, T., Tanaka, H., Nishida, Y., Obara, M., and Kimata, K. (1991). J. Cell Biol. 115: 209-221.

    The complete primary structure of type XII collagen shows a chimeric molecule with reiterated fibronectin type III motifs, von Willebrand factor A motifs, a domain homologous to a noncollagenous region of type IX collagen, and short collagenous domains with an Arg-Gly-Asp site.


    Fernandez, M. S., Dennis, J.E., Drushel, R.F., Carrino, D.A., Kimata, K., Yamagata, M., and Caplan, A.I. (1991). Dev. Biol. 147: 46-61. The dynamics of compartmentalization of embryonic muscle by extracellular matrix molecules.


    Shinomura, T., Jensen, K.L., Yamagata, M., Kimata, K., and Solursh, M. (1990). Anat. Embryol. 181: 227-233. The distribution of mesenchyme proteoglycan (PG-M) during wing bud outgrowth.


    Yamagata, M., Suzuki, S., Akiyama, S.K., Yamada, K.M., and Kimata, K. (1989). J. Biol. Chem. 264: 8012-8018. Regulation of cell-substrate adhesion by proteoglycans immobilized on extracellular substrates.


    Nishida , Y., Hata, M., Ayaki, T., Ryo, H., Yamagata, M., Shimizu, K., and Nishizuka, Y. (1988). EMBO J. 7: 775-781.

    Proliferation of both somatic and germ cells is affected in the Drosophila mutants of raf proto-oncogene.


    Yoneda, M., Yamagata, M., Suzuki, S., and Kimata, K. (1988). J. Cell Sci. 90: 265-273.

    Hyaluronic acid modulates proliferation of mouse dermal fibroblasts in culture.


    Yoneda, M., Shimizu, S., Nishi, Y., Yamagata, M., Suzuki, S., and Kimata, K. (1988). J. Cell Sci. 90: 275-286.

    Hyaluronic acid-dependent change in the extracellular matrix of mouse dermal fibroblasts that is conductive to cell proliferation.


    Yamagata, M., Kimata, K., Oike, Y., Tani, K., Maeda, N., Yoshida, K., Shimomura, Y., Yoneda, M., and Suzuki, S. (1987) J. Biol. Chem. 262: 4126-4152.

    A monoclonal antibody that specifically recognizes a glucuronic acid 2-sulfate-containing determinant in intact chondroitin sulfate chain.


    Kimata, K., Oike, Y., Tani, K., Shinomura, T., Yamagata, M., Uritani, M., and Suzuki, S. (1986) J. Biol. Chem. 261: 13517-13525.

    A large chondroitin sulfate proteoglycan (PG-M) synthesized before chondrogenesis of the limb bud of chick embryo.


    Yamagata, M., Yamada, K.M., Yoneda, M., Suzuki, S., and Kimata, K. (1986). J. Biol. Chem. 261: 13526-13535. Chondroitin sulfate proteoglycan (PG-M-like proteoglycan) is involved in the binding of hyaluronic acid to cellular fibronectin.


    About me

    Name:Masahito Yamagata



    (Nagoya University, Department of Chemistry)


    山形方人 (やまがた まさひと)


    Contact (e-mail) http://scholar.harvard.edu/masahitoyamagata  


    e-mail: yamagatm2[a]gmail.com


    My NeuroTree


    Editorial Board 
    Frontiers in Neural Circuits
    Associate Editor 2021-current
    Frontiers Research Topic Editor (Frontiers in Cellular Neuroscience, Frontiers in Neural Circuits, Frontiers in Synaptic Neuroscience, Frontiers in Molecular Neuroscience)
    "Neuroscience and Neurotechnology of Neuronal Cell Surface Molecules in Neural Circuits" 2019-2021
    Fronteirs Research Topic Editor (Frontiers in Cellular Neuroscience, Frontiers in Neural Circuits, Frontiers in Molecular Neuroscience, Frontiers in Aging Neuroscience)
    "Understanding Neural Circuits Using Single-Cell Technologies" 2021-current
    IJMS (International Journal of Molecular Sciences) Molecular Neurobiology section 2020-current
    Special Issue "Advances in the Research of Neural Circuits"
    JoVE (Guest Editor, Methods Collection "Current methods in chick embryology") 2021-current
    SynBio 2021-current
    Special Issue " Programmable proteins in synthetic biology"
    Brain Science Dictionary (The Japan Neuroscience Society)
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