VEGF/VEGFR2 signaling regulates hippocampal axon branching during development
Axon branching is crucial for proper formation of neuronal networks. Although originally identified as an angiogenic factor, VEGF also signals directly to neurons to regulate their development and function. Here we show that VEGF and its receptor VEGFR2 (also known as KDR or FLK1) are expressed in m...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-12-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/49818 |
| _version_ | 1811202805282635776 |
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| author | Robert Luck Severino Urban Andromachi Karakatsani Eva Harde Sivakumar Sambandan LaShae Nicholson Silke Haverkamp Rebecca Mann Ana Martin-Villalba Erin Margaret Schuman Amparo Acker-Palmer Carmen Ruiz de Almodóvar |
| author_facet | Robert Luck Severino Urban Andromachi Karakatsani Eva Harde Sivakumar Sambandan LaShae Nicholson Silke Haverkamp Rebecca Mann Ana Martin-Villalba Erin Margaret Schuman Amparo Acker-Palmer Carmen Ruiz de Almodóvar |
| author_sort | Robert Luck |
| collection | DOAJ |
| description | Axon branching is crucial for proper formation of neuronal networks. Although originally identified as an angiogenic factor, VEGF also signals directly to neurons to regulate their development and function. Here we show that VEGF and its receptor VEGFR2 (also known as KDR or FLK1) are expressed in mouse hippocampal neurons during development, with VEGFR2 locally expressed in the CA3 region. Activation of VEGF/VEGFR2 signaling in isolated hippocampal neurons results in increased axon branching. Remarkably, inactivation of VEGFR2 also results in increased axon branching in vitro and in vivo. The increased CA3 axon branching is not productive as these axons are less mature and form less functional synapses with CA1 neurons. Mechanistically, while VEGF promotes the growth of formed branches without affecting filopodia formation, loss of VEGFR2 increases the number of filopodia and enhances the growth rate of new branches. Thus, a controlled VEGF/VEGFR2 signaling is required for proper CA3 hippocampal axon branching during mouse hippocampus development. |
| first_indexed | 2024-04-12T02:44:46Z |
| format | Article |
| id | doaj.art-f35f5089b5394e5fb3f958611d90141c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:44:46Z |
| publishDate | 2019-12-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-f35f5089b5394e5fb3f958611d90141c2022-12-22T03:51:14ZengeLife Sciences Publications LtdeLife2050-084X2019-12-01810.7554/eLife.49818VEGF/VEGFR2 signaling regulates hippocampal axon branching during developmentRobert Luck0Severino Urban1Andromachi Karakatsani2Eva Harde3Sivakumar Sambandan4LaShae Nicholson5Silke Haverkamp6Rebecca Mann7Ana Martin-Villalba8https://orcid.org/0000-0002-9405-8910Erin Margaret Schuman9https://orcid.org/0000-0002-7053-1005Amparo Acker-Palmer10Carmen Ruiz de Almodóvar11https://orcid.org/0000-0001-5975-7815Biochemistry Center (BZH), University of Heidelberg, Heidelberg, Germany; European Center for Angioscience, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Institute for Transfusion Medicine and Immunology, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, GermanyBiochemistry Center (BZH), University of Heidelberg, Heidelberg, GermanyBiochemistry Center (BZH), University of Heidelberg, Heidelberg, Germany; European Center for Angioscience, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Institute for Transfusion Medicine and Immunology, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, GermanyInstitute of Cell Biology and Neuroscience, University of Frankfurt, Frankfurt am Main, Germany; Neurovascular Interface group, Max Planck Institute for Brain Research, Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Frankfurt am Main, GermanyDepartment of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt am Main, GermanyInstitute of Cell Biology and Neuroscience, University of Frankfurt, Frankfurt am Main, Germany; Neurovascular Interface group, Max Planck Institute for Brain Research, Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Frankfurt am Main, GermanyImaging Facility, Max Planck Institute for Brain Research, Frankfurt am Main, GermanyBiochemistry Center (BZH), University of Heidelberg, Heidelberg, GermanyDepartment of Molecular Neurobiology, German Cancer Research Center (DKFZ), Heidelberg, GermanyDepartment of Synaptic Plasticity, Max Planck Institute for Brain Research, Frankfurt am Main, GermanyInstitute of Cell Biology and Neuroscience, University of Frankfurt, Frankfurt am Main, Germany; Neurovascular Interface group, Max Planck Institute for Brain Research, Frankfurt am Main, Germany; Buchmann Institute for Molecular Life Sciences (BMLS), University of Frankfurt, Frankfurt am Main, GermanyBiochemistry Center (BZH), University of Heidelberg, Heidelberg, Germany; European Center for Angioscience, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Institute for Transfusion Medicine and Immunology, Medicine Faculty Mannheim, Heidelberg University, Heidelberg, GermanyAxon branching is crucial for proper formation of neuronal networks. Although originally identified as an angiogenic factor, VEGF also signals directly to neurons to regulate their development and function. Here we show that VEGF and its receptor VEGFR2 (also known as KDR or FLK1) are expressed in mouse hippocampal neurons during development, with VEGFR2 locally expressed in the CA3 region. Activation of VEGF/VEGFR2 signaling in isolated hippocampal neurons results in increased axon branching. Remarkably, inactivation of VEGFR2 also results in increased axon branching in vitro and in vivo. The increased CA3 axon branching is not productive as these axons are less mature and form less functional synapses with CA1 neurons. Mechanistically, while VEGF promotes the growth of formed branches without affecting filopodia formation, loss of VEGFR2 increases the number of filopodia and enhances the growth rate of new branches. Thus, a controlled VEGF/VEGFR2 signaling is required for proper CA3 hippocampal axon branching during mouse hippocampus development.https://elifesciences.org/articles/49818develomental neuroscienceaxon branchingneuro-vascular linkVEGFVEGFR2hippocampus |
| spellingShingle | Robert Luck Severino Urban Andromachi Karakatsani Eva Harde Sivakumar Sambandan LaShae Nicholson Silke Haverkamp Rebecca Mann Ana Martin-Villalba Erin Margaret Schuman Amparo Acker-Palmer Carmen Ruiz de Almodóvar VEGF/VEGFR2 signaling regulates hippocampal axon branching during development eLife develomental neuroscience axon branching neuro-vascular link VEGF VEGFR2 hippocampus |
| title | VEGF/VEGFR2 signaling regulates hippocampal axon branching during development |
| title_full | VEGF/VEGFR2 signaling regulates hippocampal axon branching during development |
| title_fullStr | VEGF/VEGFR2 signaling regulates hippocampal axon branching during development |
| title_full_unstemmed | VEGF/VEGFR2 signaling regulates hippocampal axon branching during development |
| title_short | VEGF/VEGFR2 signaling regulates hippocampal axon branching during development |
| title_sort | vegf vegfr2 signaling regulates hippocampal axon branching during development |
| topic | develomental neuroscience axon branching neuro-vascular link VEGF VEGFR2 hippocampus |
| url | https://elifesciences.org/articles/49818 |
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