{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:51:31Z","timestamp":1760143891698,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund (FWF","doi-asserted-by":"publisher","award":["T1091","P31085"],"award-info":[{"award-number":["T1091","P31085"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We recently identified PKN1 as a developmentally active gatekeeper of the transcription factor neuronal differentiation-2 (NeuroD2) in several brain areas. Since NeuroD2 plays an important role in amacrine cell (AC) and retinal ganglion cell (RGC) type formation, we aimed to study the expression of NeuroD2 in the postnatal retina of WT and Pkn1\u2212\/\u2212 animals, with a particular focus on these two cell types. We show that PKN1 is broadly expressed in the retina and that the gross retinal structure is not different between both genotypes. Postnatal retinal NeuroD2 levels were elevated upon Pkn1 knockout, with Pkn1\u2212\/\u2212 retinae showing more NeuroD2+ cells in the lower portion of the inner nuclear layer. Accordingly, immunohistochemical analysis revealed an increased amount of AC in postnatal and adult Pkn1\u2212\/\u2212 retinae. There were no differences in horizontal cell, bipolar cell, glial cell and RGC numbers, nor defective axon guidance to the optic chiasm or tract upon Pkn1 knockout. Interestingly, we did, however, see a specific reduction in SMI-32+ \u03b1-RGC in Pkn1\u2212\/\u2212 retinae. These results suggest that PKN1 is important for retinal cell type formation and validate PKN1 for future studies focusing on AC and \u03b1-RGC specification and development.<\/jats:p>","DOI":"10.3390\/ijms25052848","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T06:07:53Z","timestamp":1709273273000},"page":"2848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of PKN1 in Retinal Cell Type Formation"],"prefix":"10.3390","volume":"25","author":[{"given":"Magdalena","family":"Brunner","sequence":"first","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louisa","family":"K\u00fcnkel","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dido","family":"Weber","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motahareh Solina","family":"Safari","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-8168","authenticated-orcid":false,"given":"Gabriele","family":"Baier-Bitterlich","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2111-0757","authenticated-orcid":false,"given":"Stephanie","family":"Zur Nedden","sequence":"additional","affiliation":[{"name":"Institute of Neurobiochemistry, CCB-Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.visres.2010.07.010","article-title":"Development of the retina and optic pathway","volume":"51","author":"Reese","year":"2011","journal-title":"Vision. Res."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Peng, Y.-R. (2023). Cell-type specification in the retina: Recent discoveries from transcriptomic approaches. Curr. Opin. Neurobiol., 81.","DOI":"10.1016\/j.conb.2023.102752"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5177","DOI":"10.1523\/JNEUROSCI.0471-20.2020","article-title":"Mouse Retinal Cell Atlas: Molecular Identification of over Sixty Amacrine Cell Types","volume":"40","author":"Yan","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15778","DOI":"10.1038\/s41598-019-52215-4","article-title":"Molecular signatures of retinal ganglion cells revealed through single cell profiling","volume":"9","author":"Laboissonniere","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"111040","DOI":"10.1016\/j.celrep.2022.111040","article-title":"Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression","volume":"40","author":"Goetz","year":"2022","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1172\/JCI96165","article-title":"Protein kinase N1 critically regulates cerebellar development and long-term function","volume":"128","author":"Eith","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"640495","DOI":"10.3389\/fnsyn.2021.640495","article-title":"PKN1 Is a Novel Regulator of Hippocampal GluA1 Levels","volume":"13","author":"Safari","year":"2021","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7365","DOI":"10.1523\/JNEUROSCI.2555-10.2011","article-title":"NeuroD Factors Regulate Cell Fate and Neurite Stratification in the Developing Retina","volume":"31","author":"Cherry","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.4103\/1673-5374.355818","article-title":"Overexpressing NeuroD1 reprograms M\u00fcller cells into various types of retinal neurons","volume":"18","author":"Xu","year":"2023","journal-title":"Neural Regen. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.2859","article-title":"Neurod6 expression defines new retinal amacrine cell subtypes and regulates their fate","volume":"14","author":"Kay","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1038\/s41467-018-05134-3","article-title":"Single cell transcriptome profiling of retinal ganglion cells identifies cellular subtypes","volume":"9","author":"Rheaume","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bayam, E., Sahin, G.S., Guzelsoy, G., Guner, G., Kabakcioglu, A., and Ince-Dunn, G. (2015). Genome-wide target analysis of NEUROD2 provides new insights into regulation of cortical projection neuron migration and differentiation. BMC Genom., 16.","DOI":"10.1186\/s12864-015-1882-9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1759091414562107","DOI":"10.1177\/1759091414562107","article-title":"Connecting the retina to the brain","volume":"6","author":"Erskine","year":"2014","journal-title":"ASN Neuro"},{"key":"ref_14","first-page":"29","article-title":"Induction of a 55-kDa PKN cleavage product by ischemia\/reperfusion model in the rat retina","volume":"41","author":"Sumioka","year":"2000","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1002\/ar.1092120215","article-title":"Cell differentiation in the retina of the mouse","volume":"212","author":"Young","year":"1985","journal-title":"Anat. Rec."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lin, Y.S., Kuo, K.T., Chen, S.K., and Huang, H.S. (2018). RBFOX3\/NeuN is dispensable for visual function. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192355"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Krieger, B., Qiao, M., Rousso, D.L., Sanes, J.R., and Meister, M. (2017). Four alpha ganglion cell types in mouse retina: Function, structure, and molecular signatures. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0180091"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1054849","DOI":"10.3389\/fnana.2022.1054849","article-title":"Alpha retinal ganglion cells in pigmented mice retina: Number and distribution","volume":"16","year":"2022","journal-title":"Front. Neuroanat."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1016\/j.neuron.2015.02.017","article-title":"Subtype-specific regeneration of retinal ganglion cells following axotomy: Effects of osteopontin and mTOR signaling","volume":"85","author":"Duan","year":"2015","journal-title":"Neuron"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.neuron.2017.05.035","article-title":"Sox11 Expression Promotes Regeneration of Some Retinal Ganglion Cell Types but Kills Others","volume":"94","author":"Norsworthy","year":"2017","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"18429","DOI":"10.1074\/jbc.M113.478503","article-title":"Transcription Factors SOX4 and SOX11 Function Redundantly to Regulate the Development of Mouse Retinal Ganglion Cells*","volume":"288","author":"Jiang","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"ENEURO.0358-0320.2020","DOI":"10.1523\/ENEURO.0358-20.2020","article-title":"Posttranslational Modification of Sox11 Regulates RGC Survival and Axon Regeneration","volume":"8","author":"Chang","year":"2021","journal-title":"eNeuro"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zur Nedden, S., Safari, M.S., Fresser, F., Faserl, K., Lindner, H., Sarg, B., Baier, G., and Baier-Bitterlich, G. (2023). PKN1 Exerts Neurodegenerative Effects in an In Vitro Model of Cerebellar Hypoxic-Ischemic Encephalopathy via Inhibition of AKT\/GSK3\u03b2 Signaling. Biomolecules, 13.","DOI":"10.3390\/biom13111599"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"21022","DOI":"10.1073\/pnas.1218925110","article-title":"Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation","volume":"109","author":"Yasui","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.mcn.2010.03.006","article-title":"Transcriptional inhibition of REST by NeuroD2 during neuronal differentiation","volume":"44","author":"Ravanpay","year":"2010","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.celrep.2015.12.049","article-title":"Knockout of the PKN Family of Rho Effector Kinases Reveals a Non-redundant Role for PKN2 in Developmental Mesoderm Expansion","volume":"14","author":"Quetier","year":"2016","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1167\/iovs.12-9662","article-title":"The Rd8 Mutation of the Crb1 Gene Is Present in Vendor Lines of C57BL\/6N Mice and Embryonic Stem Cells, and Confounds Ocular Induced Mutant Phenotypes","volume":"53","author":"Mattapallil","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1167\/iovs.17-23513","article-title":"A Population Study of Common Ocular Abnormalities in C57BL\/6N rd8 Mice","volume":"59","author":"Moore","year":"2018","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.1093\/hmg\/ddg232","article-title":"CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina","volume":"12","author":"Mehalow","year":"2003","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:07:31Z","timestamp":1760105251000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/5\/2848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,29]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25052848"],"URL":"https:\/\/doi.org\/10.3390\/ijms25052848","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,2,29]]}}}