Specific fibroblast subpopulations and neuronal structures provide local sources of Vegfc-processing components during zebrafish lymphangiogenesis.

ADAMTS Proteins / genetics Animals Animals, Genetically Modified Fibroblasts / metabolism Gene Expression Regulation, Developmental HEK293 Cells Humans Lymphangiogenesis / genetics Lymphatic Vessels / embryology Microscopy, Confocal Neurons / metabolism Procollagen N-Endopeptidase / genetics Vascular Endothelial Growth Factor C / genetics Zebrafish / embryology Zebrafish Proteins / genetics

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
01 06 2020
Historique:
received: 20 12 2019
accepted: 07 05 2020
entrez: 3 6 2020
pubmed: 3 6 2020
medline: 18 8 2020
Statut: epublish

Résumé

Proteolytical processing of the growth factor VEGFC through the concerted activity of CCBE1 and ADAMTS3 is required for lymphatic development to occur. How these factors act together in time and space, and which cell types produce these factors is not understood. Here we assess the function of Adamts3 and the related protease Adamts14 during zebrafish lymphangiogenesis and show both proteins to be able to process Vegfc. Only the simultaneous loss of both protein functions results in lymphatic defects identical to vegfc loss-of-function situations. Cell transplantation experiments demonstrate neuronal structures and/or fibroblasts to constitute cellular sources not only for both proteases but also for Ccbe1 and Vegfc. We further show that this locally restricted Vegfc maturation is needed to trigger normal lymphatic sprouting and directional migration. Our data provide a single-cell resolution model for establishing secretion and processing hubs for Vegfc during developmental lymphangiogenesis.

Identifiants

DOI: 10.1038/s41467-020-16552-7 PMID: 32483144 PMC: PMC7264274
pubmed: 32483144
doi: 10.1038/s41467-020-16552-7
pii: 10.1038/s41467-020-16552-7
pmc: PMC7264274
doi:

Substances chimiques

Vascular Endothelial Growth Factor C 0
Zebrafish Proteins 0
ADAMTS Proteins EC 3.4.24.-
Procollagen N-Endopeptidase EC 3.4.24.14

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2724

Références

Tammela, T. & Alitalo, K. Lymphangiogenesis: molecular mechanisms and future promise. Cell 140, 460–476 (2010).
pubmed: 20178740 doi: 10.1016/j.cell.2010.01.045
Padberg, Y., Schulte-Merker, S. & van Impel, A. The lymphatic vasculature revisited-new developments in the zebrafish. Methods Cell Biol. 138, 221–238 (2017).
pubmed: 28129845 doi: 10.1016/bs.mcb.2016.11.001
Hogan, B. M. & Schulte-Merker, S. How to plumb a pisces: understanding vascular development and disease using zebrafish embryos. Dev. Cell 42, 567–583 (2017).
pubmed: 28950100 doi: 10.1016/j.devcel.2017.08.015
Siegfried, G. et al. The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis. J. Clin. Investig. 111, 1723–1732 (2003).
pubmed: 12782675 doi: 10.1172/JCI200317220
Joukov, V. et al. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J. 16, 3898–3911 (1997).
pubmed: 9233800 pmcid: 1170014 doi: 10.1093/emboj/16.13.3898
Hogan, B. M. et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat. Genet. 41, 396–398 (2009).
pubmed: 19287381 doi: 10.1038/ng.321
Bos, F. L. et al. CCBE1 is essential for mammalian lymphatic vascular development and enhances the lymphangiogenic effect of vascular endothelial growth factor-C in vivo. Circ. Res. 109, 486–491 (2011).
pubmed: 21778431 doi: 10.1161/CIRCRESAHA.111.250738
Jeltsch, M. et al. CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation. Circulation 129, 1962–1971 (2014).
pubmed: 24552833 doi: 10.1161/CIRCULATIONAHA.113.002779
Roukens, M. G. et al. Functional dissection of the CCBE1 protein: a crucial requirement for the collagen repeat domain. Circ Res. 116, 1660–1669 (2015).
pubmed: 25814692 doi: 10.1161/CIRCRESAHA.116.304949
Le Guen, L. et al. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. Development 141, 1239–1249 (2014).
pubmed: 24523457 doi: 10.1242/dev.100495
Janssen, L. et al. ADAMTS3 activity is mandatory for embryonic lymphangiogenesis and regulates placental angiogenesis. Angiogenesis 19, 53–65 (2016).
pubmed: 26446156 doi: 10.1007/s10456-015-9488-z
Bui, H. M. et al. Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD. J. Clin. Investig. 126, 2167–2180 (2016).
pubmed: 27159393 doi: 10.1172/JCI83967
Brouillard, P. et al. Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3. Hum. Mol. Genet. 26, 4095–4104 (2017).
pubmed: 28985353 doi: 10.1093/hmg/ddx297
van Impel, A. & Schulte-Merker, S. A fisheye view on lymphangiogenesis. Adv. Anat., Embryol. Cell Biol. 214, 153–165 (2014).
doi: 10.1007/978-3-7091-1646-3_12
Koltowska, K., Betterman, K. L., Harvey, N. L. & Hogan, B. M. Getting out and about: the emergence and morphogenesis of the vertebrate lymphatic vasculature. Development 140, 1857–1870 (2013).
pubmed: 23571211 doi: 10.1242/dev.089565
Mauri, C., Wang, G. & Schulte-Merker, S. From fish embryos to human patients: lymphangiogenesis in development and disease. Curr. Opin. Immunol. 53, 167–172 (2018).
pubmed: 29800868 doi: 10.1016/j.coi.2018.05.003
Kelwick, R., Desanlis, I., Wheeler, G. N. & Edwards, D. R. The ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs) family. Genome Biol. 16, 113 (2015).
pubmed: 26025392 pmcid: 4448532 doi: 10.1186/s13059-015-0676-3
Okuda, K. S. et al. lyve1 expression reveals novel lymphatic vessels and new mechanisms for lymphatic vessel development in zebrafish. Development 139, 2381–2391 (2012).
pubmed: 22627281 pmcid: 4074227 doi: 10.1242/dev.077701
Eng, T. C. et al. Zebrafish facial lymphatics develop through sequential addition of venous and non-venous progenitors. EMBO reports 20, e47079 (2019).
pubmed: 30877134 pmcid: 6501020 doi: 10.15252/embr.201847079
van Lessen, M. et al. Intracellular uptake of macromolecules by brain lymphatic endothelial cells during zebrafish embryonic development. eLife 6, e25932 (2017).
pubmed: 28498105 pmcid: 5457137 doi: 10.7554/eLife.25932
Galanternik, M. V. et al. A novel perivascular cell population in the zebrafish brain. Elife 6, e24369 (2017).
pmcid: 5423774 doi: 10.7554/eLife.24369
Bower, N. I. et al. Mural lymphatic endothelial cells regulate meningeal angiogenesis in the zebrafish. Nat. Neurosci. 20, 774 (2017).
pubmed: 28459441 doi: 10.1038/nn.4558
Gordon, K. et al. Mutation in vascular endothelial growth factor-C, a ligand for vascular endothelial growth factor receptor-3, is associated with autosomal dominant milroy-like primary lymphedema. Circ. Res. 112, 956–960 (2013).
pubmed: 23410910 doi: 10.1161/CIRCRESAHA.113.300350
Asakawa, K., Abe, G. & Kawakami, K. Cellular dissection of the spinal cord motor column by BAC transgenesis and gene trapping in zebrafish. Front Neural Circuits 7, 100 (2013).
pubmed: 23754985 pmcid: 3664770 doi: 10.3389/fncir.2013.00100
Myers, P. Z., Eisen, J. S. & Westerfield, M. Development and axonal outgrowth of identified motoneurons in the zebrafish. J. Neurosci. 6, 2278–2289 (1986).
pubmed: 3746410 pmcid: 6568750 doi: 10.1523/JNEUROSCI.06-08-02278.1986
Gross-Thebing, T., Paksa, A. & Raz, E. Simultaneous high-resolution detection of multiple transcripts combined with localization of proteins in whole-mount embryos. BMC Biol. 12, 55 (2014).
pubmed: 25124741 pmcid: 4172952 doi: 10.1186/s12915-014-0055-7
Ablain, J., Durand, E. M., Yang, S., Zhou, Y. & Zon, L. I. A CRISPR/Cas9 vector system for tissue-specific gene disruption in zebrafish. Dev. Cell 32, 756–764 (2015).
pubmed: 25752963 pmcid: 4379706 doi: 10.1016/j.devcel.2015.01.032
Di Donato, V. et al. 2C-Cas9: a versatile tool for clonal analysis of gene function. Genome Res. 26, 681–692 (2016).
pubmed: 26957310 pmcid: 4864464 doi: 10.1101/gr.196170.115
Wild, R. et al. Neuronal sFlt1 and Vegfaa determine venous sprouting and spinal cord vascularization. Nat. Commun. 8, 13991 (2017).
pubmed: 28071661 pmcid: 5234075 doi: 10.1038/ncomms13991
Lim, A. H. et al. Motoneurons are essential for vascular pathfinding. Development 138, 3847–3857 (2011).
pubmed: 21828101 pmcid: 3152931 doi: 10.1242/dev.068403
Covassin, L. D., Villefranc, J. A., Kacergis, M. C., Weinstein, B. M. & Lawson, N. D. Distinct genetic interactions between multiple Vegf receptors are required for development of different blood vessel types in zebrafish. Proc. Natl Acad. Sci. USA 103, 6554–6559 (2006).
pubmed: 16617120 doi: 10.1073/pnas.0506886103
Gore, A. V. et al. Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3. Development 138, 4875–4886 (2011).
pubmed: 22007135 pmcid: 3201658 doi: 10.1242/dev.068460
Goll, M. G., Anderson, R., Stainier, D. Y., Spradling, A. C. & Halpern, M. E. Transcriptional silencing and reactivation in transgenic zebrafish. Genetics 182, 747–755 (2009).
pubmed: 19433629 pmcid: 2710156 doi: 10.1534/genetics.109.102079
Akitake, C. M., Macurak, M., Halpern, M. E. & Goll, M. G. Transgenerational analysis of transcriptional silencing in zebrafish. Dev. Biol. 352, 191–201 (2011).
pubmed: 21223961 pmcid: 3065955 doi: 10.1016/j.ydbio.2011.01.002
Vanlandewijck, M. et al. A molecular atlas of cell types and zonation in the brain vasculature. Nature 554, 475–480 (2018).
pubmed: 29443965 doi: 10.1038/nature25739
Felsenfeld, A. L., Curry, M. & Kimmel, C. B. The fub-1 mutation blocks initial myofibril formation in zebrafish muscle pioneer cells. Dev. Biol. 148, 23–30 (1991).
pubmed: 1936560 doi: 10.1016/0012-1606(91)90314-S
Hatta, K., Bremiller, R., Westerfield, M. & Kimmel, C. B. Diversity of expression of engrailed-like antigens in zebrafish. Development 112, 821–832 (1991).
pubmed: 1682127
Ekker, M., Wegner, J., Akimenko, M. A. & Westerfield, M. Coordinate embryonic expression of three zebrafish engrailed genes. Development 116, 1001–1010 (1992).
pubmed: 1363539
Karpanen, T. et al. An evolutionarily conserved role for polydom/Svep1 during lymphatic vessel formation. Circ. Res 120, 1263–1275 (2017).
pubmed: 28179432 pmcid: 5389596 doi: 10.1161/CIRCRESAHA.116.308813
Cha, Y. R. et al. Chemokine signaling directs trunk lymphatic network formation along the preexisting blood vasculature. Dev. Cell 22, 824–836 (2012).
pubmed: 22516200 pmcid: 4182014 doi: 10.1016/j.devcel.2012.01.011
Morooka, N. et al. Polydom is an extracellular matrix protein involved in lymphatic vessel remodeling. Circ. Res. 120, 1276–1288 (2017).
pubmed: 28179430 doi: 10.1161/CIRCRESAHA.116.308825
Villefranc, J. A. et al. A truncation allele in vascular endothelial growth factor c reveals distinct modes of signaling during lymphatic and vascular development. Development 140, 1497–1506 (2013).
pubmed: 23462469 pmcid: 3596992 doi: 10.1242/dev.084152
Chen, J. W. & Galloway, J. L. The development of zebrafish tendon and ligament progenitors. Development 141, 2035–2045 (2014).
pubmed: 24803652 pmcid: 4011085 doi: 10.1242/dev.104067
Ma, R. C., Jacobs, C. T., Sharma, P., Kocha, K. M. & Huang, P. Stereotypic generation of axial tenocytes from bipartite sclerotome domains in zebrafish. PLoS Genet. 14, e1007775 (2018).
pubmed: 30388110 pmcid: 6235400 doi: 10.1371/journal.pgen.1007775
Tabula Muris, C. et al. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris. Nature 562, 367–372 (2018).
doi: 10.1038/s41586-018-0590-4
Alestrom, P. et al. Zebrafish: housing and husbandry recommendations. Lab. Anim. https://doi.org/10.1177/0023677219869037 (2019).
Kimmel, C. B., Ballard, W. W., Kimmel, S. R., Ullmann, B. & Schilling, T. F. Stages of embryonic development of the zebrafish. Developmental Dyn. 203, 253–310 (1995).
doi: 10.1002/aja.1002030302
van Impel, A. et al. Divergence of zebrafish and mouse lymphatic cell fate specification pathways. Development 141, 1228–1238 (2014).
pubmed: 24523456 pmcid: 3943180 doi: 10.1242/dev.105031
Bussmann, J. & Schulte-Merker, S. Rapid BAC selection for tol2-mediated transgenesis in zebrafish. Development 138, 4327–4332 (2011).
pubmed: 21865323 pmcid: 21865323 doi: 10.1242/dev.068080
Flanagan-Steet, H., Fox, M. A., Meyer, D. & Sanes, J. R. Neuromuscular synapses can form in vivo by incorporation of initially aneural postsynaptic specializations. Development 132, 4471–4481 (2005).
pubmed: 16162647 doi: 10.1242/dev.02044
Peri, F. & Nusslein-Volhard, C. Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133, 916–927 (2008).
pubmed: 18510934 doi: 10.1016/j.cell.2008.04.037
Tessadori, F. et al. Identification and functional characterization of cardiac pacemaker cells in zebrafish. PloS ONE 7, e47644 (2012).
pubmed: 23077655 pmcid: 3473062 doi: 10.1371/journal.pone.0047644
Asakawa, K. et al. Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish. Proc. Natl Acad. Sci. USA 105, 1255–1260 (2008).
pubmed: 18202183 doi: 10.1073/pnas.0704963105
Cermak, T. et al. Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting. Nucleic Acids Res. 39, e82 (2011).
pubmed: 21493687 pmcid: 3130291 doi: 10.1093/nar/gkr218
Bedell, V. M. et al. In vivo genome editing using a high-efficiency TALEN system. Nature 491, 114–118 (2012).
pubmed: 23000899 pmcid: 3491146 doi: 10.1038/nature11537
Gagnon, J. A. et al. Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS ONE 9, e98186 (2014).
pubmed: 24873830 pmcid: 4038517 doi: 10.1371/journal.pone.0098186
Hogan, B. M. et al. Vegfc/Flt4 signalling is suppressed by Dll4 in developing zebrafish intersegmental arteries. Development 136, 4001–4009 (2009).
pubmed: 19906867 doi: 10.1242/dev.039990
Schulte-Merker S. Looking at embryos. In Zebrafish: a practical approach (ed Nusslein-Volhard C). Oxford University Press (2002).
Koltowska, K. et al. Vegfc regulates bipotential precursor division and prox1 expression to promote lymphatic identity in zebrafish. Cell Rep. 13, 1828–1841 (2015).
pubmed: 26655899 doi: 10.1016/j.celrep.2015.10.055
Colige, A. et al. Domains and maturation processes that regulate the activity of ADAMTS-2, a metalloproteinase cleaving the aminopropeptide of fibrillar procollagens types I-III and V. J. Biol. Chem. 280, 34397–34408 (2005).
pubmed: 16046392 doi: 10.1074/jbc.M506458200
Picelli, S. et al. Full-length RNA-seq from single cells using Smart-seq2. Nat. Protoc. 9, 171–181 (2014).
pubmed: 24385147 doi: 10.1038/nprot.2014.006
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
pubmed: 22388286 pmcid: 22388286 doi: 10.1038/nmeth.1923
Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).
pubmed: 23618408 pmcid: 4053844 doi: 10.1186/gb-2013-14-4-r36
Liao, Y., Smyth, G. K. & Shi, W. featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930 (2014).
doi: 10.1093/bioinformatics/btt656
La Manno, G. et al. RNA velocity of single cells. Nature 560, 494–498 (2018).
pubmed: 30089906 pmcid: 6130801 doi: 10.1038/s41586-018-0414-6
Lun, A. T., McCarthy, D. J. & Marioni, J. C. A step-by-step workflow for low-level analysis of single-cell RNA-seq data with Bioconductor. F1000Res 5, 2122 (2016).
pubmed: 27909575 pmcid: 5112579
Fan, J. et al. Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis. Nat. Methods 13, 241–244 (2016).
pubmed: 4772672 pmcid: 4772672 doi: 10.1038/nmeth.3734

Auteurs

Guangxia Wang (G)

Institute for Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany.
Faculty of Medicine, WWU Münster, Münster, Germany.
Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, Germany.
ORCID: 0000-0003-4827-6498

Lars Muhl (L)

Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Huddinge, Sweden.
ORCID: 0000-0003-0952-0507

Yvonne Padberg (Y)

Institute for Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany.
Faculty of Medicine, WWU Münster, Münster, Germany.
Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, Germany.
ORCID: 0000-0001-5076-826X

Laura Dupont (L)

Laboratory of Connective Tissue Biology, GIGA, University of Liège, Liege, Belgium.

Josi Peterson-Maduro (J)

Hubrecht Institute-KNAW & UMC Utrecht, Utrecht, The Netherlands.

Martin Stehling (M)

Flow Cytometry Unit, Max Planck Institute for Molecular Biomedicine, Münster, Germany.

Ferdinand le Noble (F)

Department of Cell and Developmental Biology, Zoological Institute and Institute of Biological and Chemical Systems, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Institute of Experimental Cardiology, University of Heidelberg, Heidelberg, Germany.
DZHK (German Center for Cardiovascular Research) partner site, Heidelberg/Mannheim, Germany.

Alain Colige (A)

Laboratory of Connective Tissue Biology, GIGA, University of Liège, Liege, Belgium.

Christer Betsholtz (C)

Integrated Cardio Metabolic Centre, Department of Medicine, Karolinska Institutet, Huddinge, Sweden.
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.

Stefan Schulte-Merker (S)

Institute for Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany. schultes@ukmuenster.de.
Faculty of Medicine, WWU Münster, Münster, Germany. schultes@ukmuenster.de.
Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, Germany. schultes@ukmuenster.de.
ORCID: 0000-0003-3617-8807

Andreas van Impel (A)

Institute for Cardiovascular Organogenesis and Regeneration, WWU Münster, Münster, Germany. vanimpel@uni-muenster.de.
Faculty of Medicine, WWU Münster, Münster, Germany. vanimpel@uni-muenster.de.
Cells-in-Motion Cluster of Excellence, WWU Münster, Münster, Germany. vanimpel@uni-muenster.de.
ORCID: 0000-0002-4737-3547

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Scléroprotéines › Protéines de la matrice extracellulaire › Protéines ADAMTS › Specific fibroblast subpopulations and...
questionsmedicales.fr › Eucaryotes › Animaux › Specific fibroblast subpopulations and...
questionsmedicales.fr › Stades d'organismes › Organismes génétiquement modifiés › Animal génétiquement modifié › Specific fibroblast subpopulations and...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › Specific fibroblast subpopulations and...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes au cours du développement › Specific fibroblast subpopulations and...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Specific fibroblast subpopulations and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Specific fibroblast subpopulations and...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Morphogenèse › Lymphangiogenèse › Specific fibroblast subpopulations and...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système lymphatique › Vaisseaux lymphatiques › Specific fibroblast subpopulations and...
questionsmedicales.fr › Techniques d'investigation › Microscopie confocale › Specific fibroblast subpopulations and...
questionsmedicales.fr › Cellules › Neurones › Specific fibroblast subpopulations and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Metalloproteases › Metalloendopeptidases › Procollagen peptidase › Specific fibroblast subpopulations and...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines angiogéniques › Facteurs de croissance endothéliale vasculaire › Facteur de croissance endothéliale vasculaire de type C › Specific fibroblast subpopulations and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Poissons › Cypriniformes › Cyprinidae › Danio zébré › Specific fibroblast subpopulations and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de poisson › Protéines de poisson-zèbre › Specific fibroblast subpopulations and...