The ultimate goal of our laboratory is to achieve customized tissue regeneration and vascularization as a therapeutic intervention. Towards this goal, the main focus of our research is to understand how individual organs establish unique patterns of supporting vessel networks, namely the blood and lymphatic vasculature, for complete development of each organ system. We address this issue at the cellular and molecular level, with a particular focus on the central nervous system (CNS), at present. Controlled vascularization is a key process for organ morphogenesis as well as for the establishment of organ function. By uncovering the cellular and molecular basis of controlled vascularization during CNS development and regeneration, we hope to gain knowledge that can ultimately help design strategies for reconstituting fully vascularized, functional CNS following disease or injury.
We use zebrafish as a vertebrate model to visualize dynamic cellular processes occurring during CNS morphogenesis and vascularization in live animals. Our current focused tissue is the spinal cord, since this model allows us to further investigate the mechanisms of tissue revascularization during spinal cord regeneration. Our ongoing and future projects are aimed at defining the cellular and molecular bases of;
- Organ-Specific Vascularization and Revascularization Mechanisms
- Spatiotemporal Control of Tissue Vascularization
- Arterial, Venous, and Lymphatic Vessel Patterning
- CNS Vascular Malformations
We combine advanced techniques in cell and molecular biology, neurobiology, and microscopy to define the principles of spatiotemporally controlled vascular and lymphatic morphogenesis of the vertebrate CNS. In particular, we employ an array of powerful zebrafish molecular genetic tools, in combination with cutting-edge 3D whole-organ live imaging and genetic mosaic approaches with single-cell resolution.
- Parab S, Quick RE & Matsuoka RL. Endothelial cell type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain. Elife 10:e64295 (2021).
- Gancz D, Raftrey BC, Perlmoter G, Marín-Juez R, Semo J, Matsuoka RL, Karra R, Raviv H, Moshe N, Addadi Y, Golani O, Poss KD, Red-Horse K, Stainier DYR & Yaniv K. Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration. Elife 8:e44153 (2019).
- Mullapudi ST, Boezio GLM, Rossi A, Marass M, Matsuoka RL, Matsuda H, Helker CSM, Yang YHC & Stainier DYR. Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function. Development 146:dev.173674 (2019).
- Anbalagan S, Gordon L, Blechman J, Matsuoka RL, Rajamannar P, Wircer E, Biran J, Reuveny A, Leshkowitz D, Stainier DYR & Levkowitz G. Pituicyte cues regulate the development of permeable neuro-vascular interfaces. Developmental Cell 47:711-726 (2018).
- Matsuoka RL & Stainier DYR. Recent insights into vascular development from studies in zebrafish. Current Opinion in Hematology 25:204-211 (2018).
- Matsuoka RL, Rossi A, Stone OA & Stainier DYR. CNS-resident progenitors direct the vascularization of neighboring tissues. Proc Natl Acad Sci USA 114:10137-10142 (2017).
- Matsuoka RL, Marass M, Avdesh A, Helker CS, Maischein HM, Grosse AS, Kaur H, Lawson ND, Herzog W & Stainier DY. Radial glia regulate vascular patterning around the developing spinal cord. Elife 5:e20253 (2016).
- Sun LO, Jiang Z, Rivlin-Etzion M, Hand R, Brady C, Matsuoka RL, Yau KW, Feller MB & Kolodkin AL. On and Off Retinal Circuit Assembly by Divergent Molecular Mechanisms. Science 342:1241974 (2013).
- Matsuoka RL, Sun LO, Katayama K, Yoshida Y & Kolodkin AL. Sema6B, Sema6C, and Sema6D Expression and Function during Mammalian Retinal Development. PLOS ONE 8:e63207 (2013).
- Matsuoka RL, Jiang Z, Samuels IS, Nguyen-Ba-Charvet KT, Sun LO, Peachey NS, Chédotal A, Yau KW & Kolodkin AL. Guidance-cue control of horizontal-cell morphology, lamination, and synapse formation in the mammalian outer retina. The Journal of Neuroscience 32:6859-6868 (2012).
- Matsuoka RL, Chivatakarn O, Badea TC, Samuels IS, Cahill H, Katayama K, Kumar SR, Suto F, Chédotal A, Peachey NS, Nathans J, Yoshida Y, Giger RJ & Kolodkin AL. Class 5 transmembrane semaphorins control selective mammalian retinal lamination and function. Neuron 71:460-473 (2011).
- Matsuoka RL, Nguyen-Ba-Charvet KT, Parray A, Badea TC, Chédotal A & Kolodkin AL. Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina. Nature 470:259-263 (2011).
Ryota Matsuoka, PhD
Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Phone: (216) 442-5967
Fax: (216) 445-8204