Abstract :
[en] In the forebrain, ventrally derived oligodendrocyte precursor cells (vOPCs) travel tangentially toward the cortex together with cortical interneurons. Here, we tested in the mouse whether these populations interact during embryogenesis while migrating. By coupling histological analysis of genetic models with live imaging, we show that although they are both attracted by the chemokine Cxcl12, vOPCs and cortical interneurons occupy mutually exclusive forebrain territories enriched in this chemokine. Moreover, first-wave vOPC depletion selectively disrupts the migration and distribution of cortical interneurons. At the cellular level, we found that by promoting unidirectional contact repulsion, first-wave vOPCs steered the migration of cortical interneurons away from the blood vessels to which they were both attracted, thereby allowing interneurons to reach their proper cortical territories.
Funding text :
We thank E. Huillard (Sox10:GFP-DTA), H. Okano (Sox10:Venus), R. Franzen (Pdgfra:CreERT), and A. Pierani (Dbx1:Cre) for providing transgenic mouse lines; A. Püschel (Sema6a-Flag, Sema6c-Flag, Sema5a-Flag, Sema5b-Flag), L. Tamagnone (Sema6b-Myc, Sema6d-V5His), I. Caillé (centrin-GFP), and A. Chédotal (Sema6a) for providing plasmids; M. C. Angulo, A. Pierani, L. Tamagnone, and S. Cappello for providing feedback on the manuscript, as well as all the members of the Nguyen laboratory for their input; and S. Ormenese, A. Hego, C. Vanwinge, and R. Stephan from the GIGA-Cell Imaging and flow cytometry platforms and D. Baiwir from the GIGA-proteomics platform for technical support. All drawings were created with BioRender.com. Funding: This work was supported by the Fonds de la Recherche Scientifique (FRS) – Fonds National de la Recherche Scientifique (FNRS) (Synet; Excellence of Science grant no. 0019118F-RG36), the Fonds Leon Fredericq, the Fondation Médicale Reine Elisabeth, the Fondation Simone et Pierre Clerdent, the Belgian Science Policy (IAP-VII network P7/20), the ERANET Neuron (STEM-MCD and NeuroTalk), and the Win2Wal (ChipOmics; no. 2010126). F.L. is a Fonds pour la Formation à la Recherche dans l’Industrieet dans l’Agriculture (FRIA) doctoral fellow, M.J.-T. and J.S. are postdoctoral researchers, C.G.S. is an EOS postdoctoral fellow, and L.N. is research director at the FRS-FNRS. Author contributions: C.G.S. and L.N. conceptualized and supervised the study. F.L. designed, conceptualized, performed, and analyzed most experiments. J.S. designed, performed, and analyzed experiments to investigate the molecular mechanisms of unidirectional contact repulsion. M.J.-T. designed, performed, and analyzed molecular biology and biochemistry experiments. G.M. performed proteomic analysis. F.L., C.G.S., and L.N. wrote the manuscript with input from all authors. Competing interests: The authors declare no competing interests. Data and materials availability: All annotated data are available from the ProteomeXchange Consortium in the Proteomics Identification Database (PRIDE accession no. PXD031876). All other data are available in the main text or the supplementary materials. License information: Copyright © 2022 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www.science.org/about/science-licenses-journal-article-reuseWe thank E. Huillard (Sox10:GFP-DTA), H. Okano (Sox10:Venus), R. Franzen (Pdgfra:CreERT), and A. Pierani (Dbx1:Cre) for providing transgenic mouse lines; A. Püschel (Sema6a-Flag, Sema6c-Flag, Sema5a-Flag, Sema5b-Flag), L. Tamagnone (Sema6b-Myc, Sema6d-V5His), I. Caillé (centrin-GFP), and A. Chédotal (Sema6a) for providing plasmids; M. C. Angulo, A. Pierani, L. Tamagnone, and S. Cappello for providing feedback on the manuscript, as well as all the members of the Nguyen laboratory for their input; and S. Ormenese, A. Hego, C. Vanwinge, and R. Stephan from the GIGA-Cell Imaging and flow cytometry platforms and D. Baiwir from the GIGA-proteomics platform for technical support. All drawings were created with BioRender.com. This work was supported by the Fonds de la Recherche Scientifique (FRS) – Fonds National de la Recherche Scientifique (FNRS) (Synet; Excellence of Science grant no. 0019118F-RG36), the Fonds Leon Fredericq, the Fondation Médicale Reine Elisabeth, the Fondation Simone et Pierre Clerdent, the Belgian Science Policy (IAP-VII network P7/20), the ERANET Neuron (STEM-MCD and NeuroTalk), and the Win2Wal (ChipOmics; no. 2010126). F.L. is a Fonds pour la Formation à la Recherche dans l’Industrieet dans l’Agriculture (FRIA) doctoral fellow, M.J.-T. and J.S. are postdoctoral researchers, C.G.S. is an EOS postdoctoral fellow, and L.N. is research director at the FRS-FNRS.
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