{"doi":"10.1002/dvdy.10214","title":"Developmental expression of the HNK‐1 carbohydrate epitope on aggrecan during chondrogenesis","abstract":"<jats:title>Abstract</jats:title><jats:p>Previously, we showed that the HNK‐1 carbohydrate epitope is expressed on aggrecan synthesized in the notochord but not in mature cartilage. In the present study, we demonstrate that in immature cartilage (embryonic day 6) the HNK‐1 epitope is also expressed predominantly on aggrecan proteoglycan molecules. This finding was verified by using an aggrecan‐deficient mutant, the nanomelic chick, which lacks HNK‐1 immunostaining in the extracellular matrix of dividing and hypertrophic chondrocytes as late as embryonic day 12. By using both biochemical and immunologic approaches, the initially prominent expression of the HNK‐1 epitope is down‐regulated as development of limb and vertebral cartilage proceeds, so that by embryonic day 14 no HNK‐1 is detectable. Localization changes with development and the HNK‐1–aggrecan matrix becomes restricted to dividing and hypertrophic chondrocytes and is particularly concentrated in the intraterritorial matrix. Concomitant with the temporal and spatial decreases in HNK‐1, there is a significant increase in keratan‐sulfate content and the aggrecan‐borne HNK‐1 epitope is closely associated with proteolytic peptides that contain keratan sulfate chains, rather than chondroitin sulfate chains or carbohydrate‐free domains. Lastly, the diminution in HNK‐1 expression is consistent with a reduction in mRNA transcripts specific for at least one of the key enzymes in HNK‐1 oligosaccharide biosynthesis, the HNK‐1 sulfotransferase. These findings indicate that the HNK‐1 carbohydrate may be a common modifier of several proteoglycans (such as aggrecan) that are usually expressed early in development, and that HNK‐1 addition to these molecules may be regulated by tissue‐ and temporal‐specific expression of requisite sulfotransferases and glycosyltransferases. © 2002 Wiley‐Liss, Inc.</jats:p>","journal":"Developmental Dynamics","year":2003,"id":36626,"datarank":0.7108753120910143,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.27731954840658957,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.27731954840658957,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":14,"citers_with_citation_signal":14,"citers_with_endowment":14,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":185096,"name":"Melissa M. Mueller","orcid":null,"position":1,"is_corresponding":false},{"id":185097,"name":"Todd E. Novak","orcid":null,"position":2,"is_corresponding":false},{"id":185098,"name":"Lauren E. Schwartz","orcid":null,"position":3,"is_corresponding":false},{"id":185099,"name":"Nancy B. Schwartz","orcid":null,"position":4,"is_corresponding":false},{"id":174366,"name":"Miriam S. Domowicz","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"12508223","pmcid":null,"openalex_id":"https://openalex.org/W2053213015","authors":[],"funders":[{"funder_name":"NICHD NIH HHS","grant_id":"HD-09402","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"AR-19622","title":null}],"total_grants":2,"fwci":0.3376,"citation_percentile":0.56556451,"influential_citations":1,"citation_trend":[{"year":2014,"count":1},{"year":2016,"count":1},{"year":2018,"count":1},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"bronze","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dvdy.10214","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dvdy.10214","host_type":"BRONZE"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/dvdy.10214","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fdvdy.10214","host_type":"publisher"},{"url":"https://anatomypubs.onlinelibrary.wiley.com/doi/pdf/10.1002/dvdy.10214","host_type":"publisher"},{"url":"https://doi.org/10.1002/dvdy.10214","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/12508223","host_type":"repository"}],"fields_of_study":["Proteoglycans and glycosaminoglycans research","Cell Adhesion Molecules Research","Glycosylation and Glycoproteins Research","Biology","Medicine","Aggrecans","Amino Acid Sequence","Animals","Blotting, Western","Brain","Cartilage","Chick Embryo","Chondrocytes","Chondroitinases and Chondroitin Lyases","Cloning, Molecular","Down-Regulation","Endopeptidases","Epitopes","Extracellular Matrix Proteins","Extremities","Gene Expression Regulation, Developmental","Glucuronosyltransferase","Glycoside Hydrolases","Immunohistochemistry","In Situ Hybridization","Lectins, C-Type","Molecular Sequence Data","Oligosaccharides","Polymerase Chain Reaction","Precipitin Tests","Protein Structure, Tertiary","Proteoglycans","RNA, Messenger","Reverse Transcriptase Polymerase Chain Reaction","Sequence Homology, Amino Acid","Sulfotransferases","Time Factors","Trypsin","beta-Galactosidase"],"mesh_terms":["Amino Acid Sequence","Animals","Epitopes","beta-Galactosidase","Brain","Cartilage","Chick Embryo","Chondroitinases and Chondroitin Lyases","Cloning, Molecular","Extremities","Glycoside Hydrolases","Immunohistochemistry","Molecular Sequence Data","Oligosaccharides","Endopeptidases","Precipitin Tests","Proteoglycans","RNA, Messenger","Time Factors","Trypsin","Glucuronosyltransferase","Blotting, Western","Sulfotransferases","Down-Regulation","Polymerase Chain Reaction","Extracellular Matrix Proteins","Sequence Homology, Amino Acid","In Situ Hybridization","Protein Structure, Tertiary","Gene Expression Regulation, Developmental","Chondrocytes","Reverse Transcriptase Polymerase Chain Reaction","Lectins, C-Type","Aggrecans"],"keywords":["Aggrecan","Keratan sulfate","Epitope","Proteoglycan","Extracellular matrix","Cartilage","Biology","Biochemistry","Chondroitin sulfate","Chondroitin sulfate proteoglycan","Cell biology","Type II collagen","Molecular biology","Chemistry","Glycosaminoglycan","Immunology","Anatomy","Antigen","Osteoarthritis","Pathology","Medicine"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T16:54:36.429353Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}