{"doi":"10.1101/2020.10.13.337915","title":"Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants\n                  <jats:italic>Ift122</jats:italic>\n                  and\n                  <jats:italic>Ttc21b</jats:italic>\n                  and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.\n                </jats:p>","journal":null,"year":null,"id":685852,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":330213,"name":"Mohammed T. Islam","orcid":null,"position":1,"is_corresponding":false},{"id":328802,"name":"Kathryn V. Anderson","orcid":"0000-0003-1657-2161","position":2,"is_corresponding":false},{"id":311095,"name":"Jennifer A. Zallen","orcid":"0000-0003-3975-1568","position":3,"is_corresponding":false},{"id":328801,"name":"Eric Brooks","orcid":"0000-0003-3159-8626","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Sonic hedgehog signaling directs patterned cell remodeling during cranial neural tube closure","abstract":"<jats:title>Abstract</jats:title>\n                <jats:p>\n                  Neural tube closure defects are a major cause of infant mortality, with exencephaly accounting for nearly one-third of cases. However, the mechanisms of cranial neural tube closure are not well understood. Here we show that this process involves a tissue-wide pattern of apical constriction controlled by Sonic hedgehog (Shh) signaling. Midline cells in the mouse midbrain neuroepithelium are short with large apical surfaces, whereas lateral cells are taller and undergo synchronous apical constriction, driving neural fold elevation. Embryos lacking the Shh effector Gli2 fail to produce appropriate midline cell architecture, whereas embryos with expanded Shh signaling, including the IFT-A complex mutants\n                  <jats:italic>Ift122</jats:italic>\n                  and\n                  <jats:italic>Ttc21b</jats:italic>\n                  and embryos expressing activated Smoothened, display apical constriction defects in lateral cells. Disruption of lateral, but not midline, cell remodeling results in exencephaly. These results reveal a morphogenetic program of patterned apical constriction governed by Shh signaling that generates structural changes in the developing mammalian brain.\n                </jats:p>","is_dataset_classified":null,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26207759","pmcid":null,"openalex_id":"https://openalex.org/W3093004489","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"1F32NS098832-01","title":"Control of cell behavior during cranial neural tube closure"},{"funder_name":"National Institutes of Health","grant_id":"2P30CA008748-43","title":"MOUSE GENETICS"}],"total_grants":2,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[{"year":2025,"count":1}],"oa_status":"green","license":"CC BY","oa_locations":[{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/10/13/2020.10.13.337915.full.pdf","host_type":"repository"},{"url":"https://www.biorxiv.org/content/biorxiv/early/2020/10/13/2020.10.13.337915.full.pdf","host_type":"repository"},{"url":"https://syndication.highwire.org/content/doi/10.1101/2020.10.13.337915","host_type":"publisher"},{"url":"https://doi.org/10.1101/2020.10.13.337915","host_type":"repository"},{"url":"https://doi.org/10.7554/elife.60234","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/33103996","host_type":""},{"url":"http://dx.doi.org/10.7554/eLife.60234","host_type":""},{"url":"https://doaj.org/article/9ebcc567e1254bed8c0d7b2d095daa52","host_type":""},{"url":"https://dx.doi.org/10.1101/2020.10.13.337915","host_type":""},{"url":"https://dx.doi.org/10.7554/elife.60234","host_type":""}],"fields_of_study":["Hedgehog Signaling Pathway Studies","Developmental Biology and Gene Regulation","Epigenetics and DNA Methylation","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Neural tube","Apical constriction","Sonic hedgehog","Exencephaly","Neuroepithelial cell","Cell biology","Biology","Smoothened","Anatomy","Hedgehog signaling pathway","Neurulation","Floor plate","Neural fold","Neural plate","Morphogenesis","Neuroscience","Gastrulation","Embryo","Signal transduction","Embryogenesis","Neural stem cell","Fetus","Genetics","QH301-705.5","Science","Q","cilia","R","Brain","Mice, Inbred C57BL","Mice","neural tube defects","Neural Crest","Medicine","Animals","Hedgehog Proteins","Biology (General)","Cell Shape"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T17:50:55.566877Z","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":[]}