{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T18:16:21Z","timestamp":1774980981575,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness","award":["PI19\/01096"],"award-info":[{"award-number":["PI19\/01096"]}]},{"name":"Spanish Ministry of Economy and Competitiveness","award":["P20_00646"],"award-info":[{"award-number":["P20_00646"]}]},{"name":"Carlos III Health Institute (ISCIII)","award":["PI19\/01096"],"award-info":[{"award-number":["PI19\/01096"]}]},{"name":"Carlos III Health Institute (ISCIII)","award":["P20_00646"],"award-info":[{"award-number":["P20_00646"]}]},{"name":"European Regional Development Fund (FEDER)","award":["PI19\/01096"],"award-info":[{"award-number":["PI19\/01096"]}]},{"name":"European Regional Development Fund (FEDER)","award":["P20_00646"],"award-info":[{"award-number":["P20_00646"]}]},{"name":"Regional Department of Economy, Knowledge, Business and University, Government of Andaluc\u00eda, Andalusian Plan for Research (PAIDI-2020)","award":["PI19\/01096"],"award-info":[{"award-number":["PI19\/01096"]}]},{"name":"Regional Department of Economy, Knowledge, Business and University, Government of Andaluc\u00eda, Andalusian Plan for Research (PAIDI-2020)","award":["P20_00646"],"award-info":[{"award-number":["P20_00646"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aquaporin-4 (AQP4) expression is associated with the development of congenital hydrocephalus due to its structural role in the ependymal membrane. Gene expression analysis of periaqueductal tissue in AQP4-knockout (KO) mice at 11 days of age (P11) showed a modification in ependymal cell adhesion and ciliary protein expression that could alter cerebrospinal fluid homeostasis. A microglial subpopulation of CD11c+ cells was overexpressed in the periaqueductal tissue of mice that did not develop hydrocephalus, suggesting a possible protective effect. Here, we verified the location of this CD11c+ expression in the corpus callosum (CC) and cerebellum of AQP4-KO mice and analysed its time course. Immunofluorescence labelling of the CD11c protein in the CC and cerebellum of WT and KO animals at P3, P5, P7 and P11 confirmed an expanded presence of these cells in both tissues of the KO animal; CD11c+ cells appeared at P3 and reached a peak at P11, whereas in the WT animal, they appeared at P5, reached their peak at P7 and were undetectable by P11. The gene expression analysis in the CC samples at P11 confirmed the presence of CD11c+ microglial cells in this tissue. Among the more than 4000 overexpressed genes, Spp1 stood out with the highest differential gene expression (\u2245600), with other genes, such as Gpnmb, Itgax, Cd68 and Atp6v0d2, also identified as overexpressed. Therefore, CD11c+ cells appear to be necessary for normal corpus callosum development during postnatal life, and the absence of AQP4 prolonged its expression in this tissue.<\/jats:p>","DOI":"10.3390\/ijms25158332","type":"journal-article","created":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T17:08:34Z","timestamp":1722359314000},"page":"8332","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Absence of Aquaporin-4 (AQP4) Prolongs the Presence of a CD11c+ Microglial Population during Postnatal Corpus Callosum Development"],"prefix":"10.3390","volume":"25","author":[{"given":"Francisco","family":"Mayo","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8974-1264","authenticated-orcid":false,"given":"Lourdes","family":"Gonz\u00e1lez-Vinceiro","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Hiraldo-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Calle-Castillejo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ismael","family":"Torres-Rubio","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3904-0603","authenticated-orcid":false,"given":"Manuel","family":"Mayo","sequence":"additional","affiliation":[{"name":"F\u00edsica Te\u00f3rica, Universidad de Sevilla, Apartado de Correos 1065, 41080 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1594-0404","authenticated-orcid":false,"given":"Reposo","family":"Ram\u00edrez-Lorca","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-9428","authenticated-orcid":false,"given":"Miriam","family":"Echevarr\u00eda","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla, IBiS\/Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla, 41013 Sevilla, Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina, Universidad de Sevilla, 41009 Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ginhoux, F., Lim, S., Hoeffel, G., Low, D., and Huber, T. (2013). Origin and differentiation of microglia. Front. Cell Neurosci., 7.","DOI":"10.3389\/fncel.2013.00045"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/nature13989","article-title":"Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors","volume":"518","author":"Klapproth","year":"2015","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Benmamar-Badel, A., Owens, T., and Wlodarczyk, A. (2020). Protective Microglial Subset in Development, Aging, and Disease: Lessons From Transcriptomic Studies. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00430"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Lenz, K.M., and Nelson, L.H. (2018). Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00698"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.tins.2019.09.004","article-title":"Cien A\u00f1os de Microgl\u00eda: Milestones in a Century of Microglial Research","volume":"42","author":"Sierra","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: A field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e101997","DOI":"10.15252\/embj.2019101997","article-title":"Microglial subtypes: Diversity within the microglial community","volume":"38","author":"Stratoulias","year":"2019","journal-title":"EMBO J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuron.2018.12.006","article-title":"Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing","volume":"101","author":"Li","year":"2019","journal-title":"Neuron"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.immuni.2018.11.004","article-title":"Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41380-019-0609-8","article-title":"Microglial regional heterogeneity and its role in the brain","volume":"25","author":"Tan","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.gde.2020.06.013","article-title":"Microglial ontogeny, diversity and neurodevelopmental functions","volume":"65","author":"Thion","year":"2020","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00401-021-02389-x","article-title":"White matter microglia heterogeneity in the CNS","volume":"143","author":"Amor","year":"2022","journal-title":"Acta Neuropathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.15252\/embj.201696056","article-title":"A novel microglial subset plays a key role in myelinogenesis in developing brain","volume":"36","author":"Wlodarczyk","year":"2017","journal-title":"EMBO J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s40478-015-0203-5","article-title":"Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: A co-expression meta-analysis","volume":"3","author":"Holtman","year":"2015","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A Unique Microglia Type Associated with Restricting Development of Alzheimer\u2019s Disease","volume":"169","author":"Spinrad","year":"2017","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1016\/j.immuni.2017.08.008","article-title":"The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases","volume":"47","author":"Krasemann","year":"2017","journal-title":"Immunity"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e2116241119","DOI":"10.1073\/pnas.2116241119","article-title":"Definition of a mouse microglial subset that regulates neuronal development and proinflammatory responses in the brain","volume":"119","author":"Shen","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ghena, N.R., Anderson, S.R., Roberts, J.M., Irvin, E., Schwakopf, J., Bosco, A., and Vetter, M.L. (2024). CD11c-expressing microglia are transient, driven by interactions with apoptotic cells. bioRxiv.","DOI":"10.1101\/2024.06.24.600082"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/nn.3358","article-title":"Layer V cortical neurons require microglial support for survival during postnatal development","volume":"16","author":"Ueno","year":"2013","journal-title":"Nat. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Mayo, F., Gonz\u00e1lez-Vinceiro, L., Hiraldo-Gonz\u00e1lez, L., Calle-Castillejo, C., Morales-Alvarez, S., Ram\u00edrez-Lorca, R., and Echevarr\u00eda, M. (2023). Aquaporin-4 Expression Switches from White to Gray Matter Regions during Postnatal Development of the Central Nervous System. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033048"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Echevarr\u00eda, M., and Garc\u00eda-Miranda, P. (2024). Special Issue \u201cAquaporins in Brain Disease\u201d. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25063513"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12987-024-00548-2","article-title":"Impact of Aquaporin-4 and CD11c+ microglia in the development of ependymal cells in the aqueduct. Inferences to hydrocephalus","volume":"21","author":"Francisco","year":"2024","journal-title":"Fluids Barriers CNS"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13041-024-01098-2","article-title":"Spatiotemporal dynamics of the CD11c+ micro-glial population in the mouse brain and spinal cord from developmental to adult stages","volume":"17","author":"Nomaki","year":"2024","journal-title":"Mol. Brain"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108047","DOI":"10.1016\/j.celrep.2020.108047","article-title":"Fractalkine-Dependent Microglial Pruning of Viable Oligodendrocyte Progenitor Cells Regulates Myelination","volume":"32","author":"White","year":"2020","journal-title":"Cell Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Traiffort, E., Kassoussi, A., Zahaf, A., and Laouarem, Y. (2020). Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions. Front. Cell Neurosci., 14.","DOI":"10.3389\/fncel.2020.00079"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1007\/s00401-017-1747-1","article-title":"Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood","volume":"134","author":"Hagemeyer","year":"2017","journal-title":"Acta Neuropathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1172\/JCI77983","article-title":"TREM2 sustains microglial expansion during aging and response to demyelination","volume":"125","author":"Poliani","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1084\/jem.20141656","article-title":"Inefficient clearance of myelin debris by microglia impairs remyelinating processes","volume":"212","author":"Lampron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e42025","DOI":"10.7554\/eLife.42025","article-title":"Microglial SIRP\u03b1 regulates the emergence of CD11c+ microglia and demyelination damage in white matter","volume":"8","author":"Nozu","year":"2019","journal-title":"Elife"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.mcn.2003.12.014","article-title":"Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro","volume":"25","author":"Selvaraju","year":"2004","journal-title":"Mol. Cell Neurosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Thomas, L., and Pasquini, L.A. (2018). Galectin-3-Mediated Glial Crosstalk Drives Oligodendrocyte Differentiation and (Re)myelination. Front. Cell Neurosci., 12.","DOI":"10.3389\/fncel.2018.00297"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Trillo-Contreras, J.L., Toledo-Aral, J.J., Echevarr\u00eda, M., and Villadiego, J. (2019). AQP1 and AQP4 Contribution to Cerebrospinal Fluid Homeostasis. Cells, 8.","DOI":"10.3390\/cells8020197"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2746","DOI":"10.1016\/j.neurobiolaging.2014.06.004","article-title":"Isolation of glia from Alzheimer\u2019s mice reveals inflammation anddysfunction","volume":"35","author":"Orre","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/bioinformatics\/16.8.707","article-title":"Genetic network inference: From co-expression clustering to reverse engineering","volume":"16","author":"Liang","year":"2000","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lin, S.M., and Johnson, K.F. (2002). Methods of Microarray Data Analysis 2, Kluwer Academic Publishers.","DOI":"10.1007\/978-1-4615-0873-1"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Speed, T. (2003). Statistical analysis of gene expression microarray data. Interdisciplinary Statistics, Chapman & Hall\/CRC.","DOI":"10.1201\/9780203011232"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1109\/TKDE.2004.68","article-title":"Cluster analysis for gene expression data: A survey","volume":"16","author":"Jiang","year":"2004","journal-title":"IEEE Trans. Knowl. Data Eng."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Priness, I., Maimon, O., and Ben-Gal, I. (2007). Evaluation of gene-expression clustering via mutual information distance measure. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-111"},{"key":"ref_42","first-page":"27","article-title":"Review of the Development of Multidimensional Scaling Methods","volume":"41","author":"Mead","year":"1992","journal-title":"J. R. Stat. Society. Ser. D (Stat.)"},{"key":"ref_43","unstructured":"Green, P.E., Carmone, F.J., and Smith, S.M. (1989). Multidimensional Scaling: Concepts and Applications, Allyn and Bacon."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Borg, I., and Groenen, P. (1997). Modern Multidimensional Scaling: Theory and Applications, Springer.","DOI":"10.1007\/978-1-4757-2711-1"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cox, T.F., and Cox, M.A.A. (2000). Multidimensional Scaling, CRC Press. [2nd ed.].","DOI":"10.1201\/9781420036121"},{"key":"ref_46","first-page":"7","article-title":"Gene expression analysis via multidimensional scaling","volume":"7","author":"Chen","year":"2005","journal-title":"Curr. Protoc. Bioinform."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8332\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:26:31Z","timestamp":1760109991000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/15\/8332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,30]]},"references-count":46,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25158332"],"URL":"https:\/\/doi.org\/10.3390\/ijms25158332","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,30]]}}}