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Mutations in BM genes can affect this structural support and are often associated with human diseases, including fibrosis, diabetes, and cancer, and are considered a hallmark of aging. However, how the BM maintains this support in organs with constant mechanical stress is largely unknown. In the Drosophila ovary, the BM provides the mechanical cues that are required for egg development. We discovered that the glycoprotein Ndg is important for maintaining organ integrity during egg production. Loss of Ndg results in a reduced number of progeny due to unfertilized eggs. Furthermore, we observed a decreased number of developing eggs and a premature death of egg chambers during development. Our results suggest that Ndg plays an important role in fertility.<\/jats:p>","DOI":"10.3390\/biology14091192","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T10:55:37Z","timestamp":1756983337000},"page":"1192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Nidogen in Reproductive Fitness in Drosophila"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0278-6580","authenticated-orcid":false,"given":"Uwe","family":"T\u00f6pfer","sequence":"first","affiliation":[{"name":"Institut fuer Allgemeine Zoologie und Entwicklungsbiologie, Fachbereich 08 Biologie und Chemie, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 38, 35392 Giessen, Germany"},{"name":"Department of Biology, Developmental Genetics, Philipps University, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7028-6548","authenticated-orcid":false,"given":"Anne","family":"Holz","sequence":"additional","affiliation":[{"name":"Institut fuer Allgemeine Zoologie und Entwicklungsbiologie, Fachbereich 08 Biologie und Chemie, Justus-Liebig-Universitaet Giessen, Heinrich-Buff-Ring 38, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"bio059980","DOI":"10.1242\/bio.059980","article-title":"Basement Membrane Dynamics and Mechanics in Tissue Morphogenesis","volume":"12","year":"2023","journal-title":"Biol. 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Migr."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6846","DOI":"10.1128\/MCB.25.15.6846-6856.2005","article-title":"Compound Genetic Ablation of Nidogen 1 and 2 Causes Basement Membrane Defects and Perinatal Lethality in Mice","volume":"25","author":"Bader","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dai, J., Estrada, B., Jacobs, S., S\u00e1nchez-S\u00e1nchez, B.J., Tang, J., Ma, M., Magad\u00e1n-Corpas, P., Pastor-Pareja, J.C., and Mart\u00edn-Bermudo, M.D. (2018). Dissection of Nidogen Function in Drosophila Reveals Tissue-Specific Mechanisms of Basement Membrane Assembly. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007483"},{"key":"ref_7","first-page":"dev168948","article-title":"Characterization of Drosophila Nidogen\/Entactin Reveals Roles in Basement Membrane Stability, Barrier Function and Nervous System Patterning","volume":"146","author":"Wolfstetter","year":"2019","journal-title":"Development"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"T\u00f6pfer, U., and Holz, A. (2024). Nidogen in Development and Disease. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1380542"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1097\/01.LAB.0000042240.52093.0F","article-title":"Neurologic Defects and Selective Disruption of Basement Membranes in Mice Lacking Entactin-1\/Nidogen-1","volume":"82","author":"Dong","year":"2002","journal-title":"Lab. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7007","DOI":"10.1128\/MCB.20.18.7007-7012.2000","article-title":"The Absence of Nidogen 1 Does Not Affect Murine Basement Membrane Formation","volume":"20","author":"Murshed","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6820","DOI":"10.1128\/MCB.22.19.6820-6830.2002","article-title":"Gene Structure and Functional Analysis of the Mouse Nidogen-2 Gene: Nidogen-2 Is Not Essential for Basement Membrane Formation in Mice","volume":"22","author":"Schymeinsky","year":"2002","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"39620","DOI":"10.1074\/jbc.M607886200","article-title":"Loss of Nidogen-1 and -2 Results in Syndactyly and Changes in Limb Development","volume":"281","author":"Nischt","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1091\/mbc.11.11.3911","article-title":"Nidogen Is Nonessential and Not Required for Normal Type IV Collagen Localization in Caenorhabditis elegans","volume":"11","author":"Kang","year":"2000","journal-title":"Mol. Biol. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3577","DOI":"10.1523\/JNEUROSCI.23-09-03577.2003","article-title":"The Basement Membrane Components Nidogen and Type XVIII Collagen Regulate Organization of Neuromuscular Junctions in Caenorhabditis elegans","volume":"23","author":"Ackley","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/S0959-4388(03)00002-3","article-title":"Development and Maintenance of Neuronal Architecture at the Ventral Midline of C. elegans","volume":"13","author":"Hobert","year":"2003","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1126\/science.288.5463.150","article-title":"Positioning of Longitudinal Nerves in C. elegans by Nidogen","volume":"288","author":"Kim","year":"2000","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.jgg.2017.09.011","article-title":"Short Body Length Phenotype Is Compensated by the Upregulation of Nidogen Family Members in a Deleterious Nid1a Mutation of Zebrafish","volume":"44","author":"Zhu","year":"2017","journal-title":"J. Genet. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"18908","DOI":"10.1016\/S0021-9258(19)37047-4","article-title":"The Receptor for the Basement Membrane Glycoprotein Entactin Is the Integrin Alpha 3\/Beta 1","volume":"267","author":"Dedhar","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15838","DOI":"10.1074\/jbc.270.26.15838","article-title":"Two Distinct Cell Attachment Sites in Entactin Are Revealed by Amino Acid Substitutions and Deletion of the RGD Sequence in the Cysteine-Rich Epidermal Growth Factor Repeat 2","volume":"270","author":"Dong","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2508057","DOI":"10.1080\/2162402X.2025.2508057","article-title":"Loss of the Extracellular Protease ADAMTS1 Reveals an Antitumorigenic Program Involving the Action of NIDOGEN-1 on Macrophage Polarization","volume":"14","author":"Ricciardelli","year":"2025","journal-title":"OncoImmunology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.1634\/stemcells.2007-0991","article-title":"A Stable Niche Supports Long-Term Maintenance of Human Epidermal Stem Cells in Organotypic Cultures","volume":"26","author":"Muffler","year":"2008","journal-title":"Stem Cells"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Vanhooren, J., Deneweth, L., Pagliaro, L., Ren, Z., Giaimo, M., Zamponi, R., Roti, G., Depreter, B., Hofmans, M., and De Moerloose, B. (2025). Nidogen-1, a Player in KMT2A-Rearranged Pediatric Acute Myeloid Leukemia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073011"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lan, Z., Xiao, Y., Liao, Y., Li, X., Zhang, Y., Wang, H., and Zhang, W. (2025). NID2 Affects Prognosis of Glioma via Activating the Akt Signaling Pathway. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26083859"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kathuria, I., Prasad, A., Sharma, B.K., Aithabathula, R.V., Ofosu-Boateng, M., Gyamfi, M.A., Jiang, J., Park, F., Singh, U.P., and Singla, B. (2024). Nidogen 2 Overexpression Promotes Hepatosteatosis and Atherosclerosis. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202410.2083.v1"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"iyad211","DOI":"10.1093\/genetics\/iyad211","article-title":"FlyBase: Updates to the Drosophila Genes and Genomes Database","volume":"227","author":"Marygold","year":"2024","journal-title":"Genetics"},{"key":"ref_26","unstructured":"Spradling, A.C. (1993). Developmental Genetics of Oogenesis. The Development of Drosophila Melanogaster, Cold Spring Harbor Laboratory Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ydbio.2007.11.029","article-title":"Mononuclear Muscle Cells in Drosophila Ovaries Revealed by GFP Protein Traps","volume":"314","author":"Hudson","year":"2008","journal-title":"Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dev200456","DOI":"10.1242\/dev.200456","article-title":"Distinct Contributions of ECM Proteins to Basement Membrane Mechanical Properties in Drosophila","volume":"149","author":"Dahmann","year":"2022","journal-title":"Development"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1186\/gb-2012-13-3-r21","article-title":"The Generation of Chromosomal Deletions to Provide Extensive Coverage and Subdivision of the Drosophila melanogaster Genome","volume":"13","author":"Cook","year":"2012","journal-title":"Genome Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15050","DOI":"10.1073\/pnas.261408198","article-title":"A Protein Trap Strategy to Detect GFP-Tagged Proteins Expressed from Their Endogenous Loci in Drosophila","volume":"98","author":"Morin","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","unstructured":"Ashburner, M. (1989). Drosophila: A Laboratory Handbook, Cold Spring Harbor Laboratory."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/j.mod.2009.05.001","article-title":"Fusion of Circular and Longitudinal Muscles in Drosophila Is Independent of the Endoderm but Further Visceral Muscle Differentiation Requires a Close Contact between Mesoderm and Endoderm","volume":"126","author":"Wolfstetter","year":"2009","journal-title":"Mech. Dev."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Lebo, D.P.V., and McCall, K. (2021). Murder on the Ovarian Express: A Tale of Non-Autonomous Cell Death in the Drosophila Ovary. Cells, 10.","DOI":"10.3390\/cells10061454"},{"key":"ref_34","unstructured":"R Core Team (2021). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_35","unstructured":"T\u00f6pfer, U. (2019). Analysen zur Regulation und Komposition der Extrazellul\u00e4ren Matrix von Drosophila melanogaster. [Ph.D. Thesis, University of Gie\u00dfen]."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/j.1432-1033.1989.tb15013.x","article-title":"Binding of Nidogen and the Laminin-Nidogen Complex to Basement Membrane Collagen Type IV","volume":"184","author":"Aumailley","year":"1989","journal-title":"Eur. J. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1002\/j.1460-2075.1989.tb03349.x","article-title":"Amino Acid Sequence of Mouse Nidogen, a Multidomain Basement Membrane Protein with Binding Activity for Laminin, Collagen IV and Cells","volume":"8","author":"Mann","year":"1989","journal-title":"EMBO J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1006\/jmbi.2001.4878","article-title":"Mapping of Binding Sites for Nidogens, Fibulin-2, Fibronectin and Heparin to Different IG Modules of Perlecan1","volume":"311","author":"Hopf","year":"2001","journal-title":"J. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.matbio.2025.06.003","article-title":"ECM Proteins Shape Topographical Patterns in the Basement Membrane of Drosophila Wing Discs","volume":"140","author":"Dahmann","year":"2025","journal-title":"Matrix Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.devcel.2020.06.005","article-title":"Rapid Homeostatic Turnover of Embryonic ECM during Tissue Morphogenesis","volume":"54","author":"Matsubayashi","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.devcel.2020.05.022","article-title":"Comprehensive Endogenous Tagging of Basement Membrane Components Reveals Dynamic Movement within the Matrix Scaffolding","volume":"54","author":"Keeley","year":"2020","journal-title":"Dev. Cell"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15476278.2015.1019687","article-title":"Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression","volume":"11","author":"Handorf","year":"2015","journal-title":"Organogenesis"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.celrep.2015.09.008","article-title":"Companion Blood Cells Control Ovarian Stem Cell Niche Microenvironment and Homeostasis","volume":"13","author":"Zimniak","year":"2015","journal-title":"Cell Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.devcel.2013.12.016","article-title":"The Hox Gene Abd-B Controls Stem Cell Niche Function in the Drosophila Testis","volume":"28","author":"Papagiannouli","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pearson, J.R., Zurita, F., Tom\u00e1s-Gallardo, L., D\u00edaz-Torres, A., Loza, M.D.C.D., Franze, K., Mart\u00edn-Bermudo, M.D., and Gonz\u00e1lez-Reyes, A. (2016). ECM-Regulator Timp Is Required for Stem Cell Niche Organization and Cyst Production in the Drosophila Ovary. PLoS Genet., 12.","DOI":"10.1371\/journal.pgen.1005763"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ncb1660","article-title":"Integrin-Dependent Anchoring of a Stem-Cell Niche","volume":"9","author":"Tanentzapf","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.semcdb.2018.02.019","article-title":"Activating Embryonic Development in Drosophila","volume":"84","year":"2018","journal-title":"Semin. Cell Dev. Biol."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:39:18Z","timestamp":1760035158000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/14\/9\/1192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,4]]},"references-count":47,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["biology14091192"],"URL":"https:\/\/doi.org\/10.3390\/biology14091192","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2025,9,4]]}}}