Taija Mäkinen – Regulation of the lymphatic vasculature
The aim of our research is to understand how lymphatic vessels are formed and to gain insight into the mechanisms that underlie lymphatic disorders.

The lymphatic vasculature constitutes a network of vessels critical for the maintenance of the body’s fluid balance. Failure of lymphatic vessels can lead to a disabling disease called lymphoedema for which there is no cure or effective treatment.
Emerging evidence shows that the lymphatic vasculature plays critical roles, beyond passive transport of fluid, in important physiological processes and common diseases. Understanding mechanisms of lymphangiogenesis may thus enable development of new therapies for common diseases that affect a large number of people worldwide.
Our laboratory aims to understand how endothelial cells lining lymphatic vessels integrate signals from multiple sources in a complex tissue environment to coordinate vascular morphogenesis and functional specialisation. We also investigate how regulators of developmental (lymph)angiogenesis impact genetic human diseases such as lymphoedema and vascular malformations, and how endothelial cells and vessels contribute to various diseases.
For more information about our research, see www.makinenlab.com
Group members
Publications
Intravital Imaging of Disease Mechanisms in a Mouse Model of CCM Skin Lesions-Brief Report
Part of Arteriosclerosis, Thrombosis and Vascular Biology, p. 113-118, 2025
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iSuRe-HadCre is an essential tool for effective conditional genetics
Part of Nucleic Acids Research, 2024
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Lymphatic malformations: mechanistic insights and evolving therapeutic frontiers
Part of Journal of Clinical Investigation, 2024
- DOI for Lymphatic malformations: mechanistic insights and evolving therapeutic frontiers
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Penile cavernous sinusoids are Prox1-positive hybrid vessels
Part of Vascular Biology, 2024
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Specialized post-arterial capillaries facilitate adult bone remodelling
Part of Nature Cell Biology, 2024
- DOI for Specialized post-arterial capillaries facilitate adult bone remodelling
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Part of Haematologica, p. 772-784, 2023
- DOI for APOLD1 loss causes endothelial dysfunction involving cell junctions, cytoskeletal architecture, and Weibel-Palade bodies, while disrupting hemostasis
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Hemogenic activity of lymphatic endothelium unleashed
Part of Nature Cardiovascular Research, p. 230-231, 2023
Part of Journal of Experimental Medicine, 2023
- DOI for Immune-interacting lymphatic endothelial subtype at capillary terminals drives lymphatic malformation
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Part of Frontiers in Physiology, 2023
- DOI for Mapping the lymphatic system across body scales and expertise domains: A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium
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Molecular anatomy of adult mouse leptomeninges
Part of Neuron, 2023
- DOI for Molecular anatomy of adult mouse leptomeninges
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Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells
Part of JCI Insight, 2022
- DOI for Angiogenesis depends upon EPHB4-mediated export of collagen IV from vascular endothelial cells
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Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing
Part of Life Science Alliance, 2022
- DOI for Cdh5-lineage–independent origin of dermal lymphatics shown by temporally restricted lineage tracing
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Cellular Origin of Sporadic CCMs
Part of New England Journal of Medicine, p. 1291-1291, 2022
Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
Part of Journal of Clinical Investigation, 2022
- DOI for Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression
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Part of Stem Cell Reports, p. 1089-1104, 2022
An inducible Cldn11-CreERT2 mouse line for selective targeting of lymphatic valves
Part of Genesis, 2021
- DOI for An inducible Cldn11-CreERT2 mouse line for selective targeting of lymphatic valves
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Homeostatic maintenance of the lymphatic vasculature
Part of Trends in Molecular Medicine, p. 955-970, 2021
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Lymphatic Malformations: Genetics, Mechanisms and Therapeutic Strategies
Part of Circulation Research, p. 136-154, 2021
Mutations in EPHB4 cause human venous valve aplasia
Part of JCI Insight, 2021
- DOI for Mutations in EPHB4 cause human venous valve aplasia
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Transcription factor FOXP2 is a flow-induced regulator of collecting lymphatic vessels
Part of EMBO Journal, 2021
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Part of Journal of Experimental Medicine, 2021
Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation
Part of Nature Communications, 2020
- DOI for Blockade of VEGF-C signaling inhibits lymphatic malformations driven by oncogenic PIK3CA mutation
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Part of eLIFE, 2020
- DOI for EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity
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Part of Transgenic research, p. 53-68, 2020
- DOI for Tamoxifen-independent recombination of reporter genes limits lineage tracing and mosaic analysis using CreER(T2) lines
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Gut microbiota regulates lacteal integrity by inducing VEGF-C in intestinal villus macrophages
Part of EMBO Reports, 2019
Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth
Part of EMBO Journal, 2019
Neurobiology: A Drain At The Base Of The Brain
Part of Nature, p. 34-35, 2019
YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis
Part of Circulation Research, p. 225-242, 2019
Distinct roles of VE-cadherin for development and maintenance of specific lymph vessel beds
Part of EMBO Journal, 2018
Genetic Lineage Tracing of Lymphatic Endothelial Cells in Mice.
Part of Methods in Molecular Biology, p. 37-53, 2018
Part of Nature Communications, 2018
- DOI for Heterogeneity in VEGFR3 levels drives lymphatic vessel hyperplasia through cell-autonomous and non-cell-autonomous mechanisms
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Part of Nature Communications, 2018
- DOI for Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program
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PROX1 is a transcriptional regulator of MMP14
Part of Scientific Reports, 2018
- DOI for PROX1 is a transcriptional regulator of MMP14
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Part of Development, 2018
Part of Arteriosclerosis, Thrombosis and Vascular Biology, p. 1732-1735, 2017
Human venous valve disease caused by mutations in FOXC2 and GJC2
Part of Journal of Experimental Medicine, p. 2437-2452, 2017
- DOI for Human venous valve disease caused by mutations in FOXC2 and GJC2
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Human Venous Valve Disease Caused by Mutations in FOXC2 and GJC2
Part of Journal of Vascular Research, p. 62-62, 2017
Lymphangiogenesis guidance by paracrine and pericellular factors
Part of Genes & Development, p. 1615-1634, 2017
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Mechanisms underlying human venous valve disease caused by mutations in Foxc2 and connexin47
Part of British Journal of Surgery, p. 8-8, 2017
Part of Development, p. 3590-3601, 2017
Vascular heterogeneity and specialization in development and disease
Part of Nature reviews. Molecular cell biology, p. 477-494, 2017
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EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis
Part of Journal of Clinical Investigation, p. 3080-3088, 2016
- DOI for EPHB4 kinase-inactivating mutations cause autosomal dominant lymphatic-related hydrops fetalis
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Heterogeneity in the lymphatic vascular system and its origin
Part of Cardiovascular Research, p. 310-321, 2016
- DOI for Heterogeneity in the lymphatic vascular system and its origin
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Lymphatic System in Cardiovascular Medicine
Part of Circulation Research, p. 515-530, 2016
Pdgfrb-Cre targets lymphatic endothelial cells of both venous and non-venous origins
Part of Genesis, p. 350-358, 2016
Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system
Part of Angiogenesis, p. 433-445, 2016
- DOI for Vegfr3-CreER (T2) mouse, a new genetic tool for targeting the lymphatic system
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A Transgenic Prox1-Cre-tdTomato Reporter Mouse for Lymphatic Vessel Research
Part of PLOS ONE, 2015
- DOI for A Transgenic Prox1-Cre-tdTomato Reporter Mouse for Lymphatic Vessel Research
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cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels
Part of Cell Reports, p. 1708-1721, 2015
- DOI for cKit Lineage Hemogenic Endothelium-Derived Cells Contribute to Mesenteric Lymphatic Vessels
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FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature
Part of Journal of Clinical Investigation, p. 3861-3877, 2015
Nonvenous Origin of Dermal Lymphatic Vasculature
Part of Circulation Research, p. 1649-1654, 2015
Organ-Specific Origins of Lymphatic Vasculature
Part of Journal of Vascular Research, p. 18-19, 2015
Part of Nature Communications, 2015
Therapeutic Insights to Lymphangiogenic Growth Factors
Part of Journal of Vascular Research, p. 19-19, 2015
VEGFR3 does not sustain retinal angiogenesis without VEGFR2
Part of Proceedings of the National Academy of Sciences of the United States of America, p. 761-766, 2015
Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity
Part of Journal of Clinical Investigation, p. 3960-3974, 2014
Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life.
Part of Journal of Clinical Investigation, 2014
The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel
Part of Journal of Clinical Investigation, p. 3975-3986, 2014
Adrenomedullin haploinsufficiency predisposes to secondary lymphedema.
Part of Journal of Investigative Dermatology, 2013
Flow control in our vessels: vascular valves make sure there is no way back.
Part of Cellular and Molecular Life Sciences (CMLS), 2013
Part of Developmental Cell, 2013
Part of Experimental Cell Research, p. 1618-1625, 2013
Blood flow reprograms lymphatic vessels to blood vessels.
Part of Journal of Clinical Investigation, 2012
Part of Developmental Cell, 2012
Part of American Journal of Human Genetics, 2012
Part of Developmental Dynamics, p. 770-786, 2012
Part of Journal of Cell Biology, 2012
Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice.
Part of Journal of Clinical Investigation, 2011
Part of Journal of Vascular Research, 2011
Part of Nature Genetics, 2011
Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis.
Part of Genes & Development, 2011
VEGFR-3 controls tip to stalk conversion at vessel fusion sites by reinforcing Notch signalling.
Part of Nature Cell Biology, 2011
EphB-ephrin-B2 interactions are required for thymus migration during organogenesis.
Part of Proceedings of the National Academy of Sciences of the United States of America, 2010
Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis.
Part of Nature, 2010
Lymphatic dysfunction, not aplasia, underlies Milroy disease.
Part of Microcirculation, 2010
Integrin-alpha9 is required for fibronectin matrix assembly during lymphatic valve morphogenesis.
Part of Developmental Cell, 2009
Part of Molecular and Cellular Biology, 2008
Lymphangiogenesis in development and disease.
Part of Novartis Foundation symposium, 2007
Lymphatic vasculature: a molecular perspective.
Part of Bioessays, 2007
Molecular mechanisms of lymphatic vascular development.
Part of Cellular and Molecular Life Sciences (CMLS), 2007
Part of Journal of Neuroscience, 2006
Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation.
Part of American Journal of Pathology, 2006
Regulation of lymphangiogenesis--from cell fate determination to vessel remodeling.
Part of Experimental Cell Research, 2006
Neural guidance molecules regulate vascular remodeling and vessel navigation.
Part of Genes & Development, 2005
PDZ interaction site in ephrinB2 is required for the remodeling of lymphatic vasculature.
Part of Genes & Development, 2005
Part of Nature Genetics, 2004
Part of Cancer Research, 2004
Vegfc is required for vascular development and endoderm morphogenesis in zebrafish.
Part of EMBO Reports, 2004
Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function.
Part of The FASEB Journal, 2003
Part of Journal of Biological Chemistry, p. 40973-40979, 2003
Part of J Biol Chem, p. 40973, 2003
Part of Proceedings of the National Academy of Sciences of the United States of America, 2002
Part of EMBO Journal, 2002
Lymphatic endothelium: a new frontier of metastasis research.
Part of Nature Cell Biology, 2002
[Lymphatic growth factors play a part in metastasis formation].
Part of Duodecim, 2002
Molecular mechanisms of lymphangiogenesis.
Part of Cold Spring Harbor Symposia on Quantitative Biology, 2002
Part of Nature Medicine, 2001
Part of EMBO Journal, 2001
Part of EMBO Journal, 2001
Part of European Journal of Biochemistry, 2000
Part of Journal of Biological Chemistry, 1999