Ryota Matsuoka Laboratory

Research

Genetic Dissection of CNS Vascular Heterogeneity, Specializations, and Integrity in Health and Disease

Molecular Genetics of CNS Blood and Lymphatic Vascular Specializations and Brain Barrier Development

A research goal in my laboratory is to elucidate the complex genetic mechanisms that build the mature central nervous system (CNS). During animal development, organ growth is intimately coordinated with the establishment of supporting vessel networks, the blood and lymphatic vasculature. Each organ establishes unique patterns/properties of blood and lymphatic vascular networks that are essential for organ-specific function. Our research aims to uncover key determinants of organ-specific blood and lymphatic vascular specializations with a focus on the CNS.

Structural and functional heterogeneity of brain vasculature has been recognized for over a century and is known to be important for mediating brain region-specific neural function. However, it still remains unknown how this vessel heterogeneity emerges. We employ zebrafish as a model organism and combine modern genetics with high-resolution 3D imaging to address how vascular phenotypic heterogeneity arises in distinct regions of the CNS, using the choroid plexus, hypothalamus-pituitary, pineal gland, retina, spinal cord, and meninges as vertebrate model systems. Our current investigations focus on examining two major types of brain endothelial cells: those that form the semi-permeable blood-brain barrier and those that develop permeable fenestrae. Our future studies aim to identify a spectrum of genes involved in vascular endothelial cell identities and heterogeneity in the CNS.

Numerous neurological diseases involve blood and lymphatic vascular abnormalities, and abrogated vascular properties can exacerbate neuroinflammation and subsequently neurodegeneration associated with aging and diseases. We expect that a better understanding of molecular pathways involved in CNS blood and lymphatic vascular health and disease would help prevent or treat neural and vascular abnormalities following injury/disease. Therefore, our ultimate goal is to translate our research activities into therapeutic strategies that would enable CNS region-specific and vessel type-selective vascular therapies for the treatment of devastating neurological diseases.

Selected Publications

View publications for Ryota Matsuoka, PhD
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1. Lee NJ, Parab S, Lam AE, Leong JX & Matsuoka RL (2024).  A molecular mechanism for blood-brain barrier and fenestrated vessel segregation from a multipotent cerebrovascular niche.  Preprint: bioRxiv 2024.12.10.627641; doi: https://doi.org/10.1101/2024.12.10.627641.
2. Lee NJ & Matsuoka RL (2024).  Generation of brain vascular heterogeneity: recent advances from the perspective of angiogenesis.  Neural Regeneration Research 20:2013-2014.
3. Lee NJ & Matsuoka RL (2024).  CRISPR/Cas9-based mutagenesis strategies for efficient biallelic gene inactivation and consistent phenotypic detection in F0 zebrafish.  Methods in Molecular Biology, in press.
4. Parab S, Card OA, Chen Q, America M, Buck LD, Quick RE, Horrigan WF, Levkowitz G, Vanhollebeke B & Matsuoka RL (2023).  Local angiogenic interplay of Vegfc/d and Vegfa controls brain region-specific emergence of fenestrated capillaries.  Elife 12:e86066.
5. Matsuoka RL, Buck LD, Vajrala KP, Quick RE & Card OA (2022).  Historical and current perspectives on blood endothelial cell heterogeneity in the brain.  Cell Mol Life Sci 79:372.
6. Quick RE, Buck LD, Parab S, Tolbert ZR & Matsuoka RL (2021).  Highly efficient synthetic CRISPR RNA/Cas9-based mutagenesis for rapid cardiovascular phenotypic screening in F0 zebrafish.  Front. Cell Dev. Biol. 9:735598.
7. Liu KC, Villasenor A, Bertuzzi M, Schmitner N, Radros N, Rautio L, Mattonet K, Matsuoka RL, Reischauer S, Stainier DYR & Andersson O (2021).  Insulin-producing β-cells regenerate ectopically from a mesodermal origin under the perturbation of hemato-endothelial specification.  Elife 10:e65758.
8. Parab S, Quick RE & Matsuoka RL (2021).  Endothelial cell-type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain.  Elife 10:e64295.
9. 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 (2019).  Distinct origins and molecular mechanisms contribute to lymphatic formation during cardiac growth and regeneration.  Elife 8:e44153.
10. Mullapudi ST, Boezio GLM, Rossi A, Marass M, Matsuoka RL, Matsuda H, Helker CSM, Yang YHC & Stainier DYR (2019).  Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function.  Development 146:dev.173674.
11. Anbalagan S, Gordon L, Blechman J, Matsuoka RL, Rajamannar P, Wircer E, Biran J, Reuveny A, Leshkowitz D, Stainier DYR & Levkowitz G (2018).  Pituicyte cues regulate the development of permeable neuro-vascular interfaces.  Developmental Cell 47:711-726.
12. Matsuoka RL & Stainier DYR (2018).  Recent insights into vascular development from studies in zebrafish.  Current Opinion in Hematology 25:204-211.
13. Matsuoka RL, Rossi A, Stone OA & Stainier DYR (2017).  CNS-resident progenitors direct the vascularization of neighboring tissues.  Proc Natl Acad Sci USA 114:10137-10142.
14. Matsuoka RL, Marass M, Avdesh A, Helker CS, Maischein HM, Grosse AS, Kaur H, Lawson ND, Herzog W & Stainier DY (2016).  Radial glia regulate vascular patterning around the developing spinal cord.  Elife 5:e20253.
15. Sun LO, Jiang Z, Rivlin-Etzion M, Hand R, Brady C, Matsuoka RL, Yau KW, Feller MB & Kolodkin AL (2013).  On and Off Retinal Circuit Assembly by Divergent Molecular Mechanisms.  Science 342:1241974.
16. Matsuoka RL, Sun LO, Katayama K, Yoshida Y & Kolodkin AL (2013).  Sema6B, Sema6C, and Sema6D Expression and Function during Mammalian Retinal Development.  PLOS ONE 8:e63207.
17. Matsuoka RL, Jiang Z, Samuels IS, Nguyen-Ba-Charvet KT, Sun LO, Peachey NS, Chédotal A, Yau KW & Kolodkin AL (2012).  Guidance-cue control of horizontal-cell morphology, lamination, and synapse formation in the mammalian outer retina.  The Journal of Neuroscience 32:6859-6868.
18. 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 (2011).  Class 5 transmembrane semaphorins control selective mammalian retinal lamination and function.  Neuron 71:460-473.
19. Matsuoka RL, Nguyen-Ba-Charvet KT, Parray A, Badea TC, Chédotal A & Kolodkin AL (2011).  Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina.  Nature 470:259-263.