{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:46:37Z","timestamp":1791999997410,"version":"4.4.0"},"reference-count":58,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,27]],"date-time":"2022-11-27T00:00:00Z","timestamp":1669507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["7222016"],"award-info":[{"award-number":["7222016"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["CXYJ-2021-03"],"award-info":[{"award-number":["CXYJ-2021-03"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation of Capital Institute of Pediatrics","award":["7222016"],"award-info":[{"award-number":["7222016"]}]},{"name":"Research Foundation of Capital Institute of Pediatrics","award":["CXYJ-2021-03"],"award-info":[{"award-number":["CXYJ-2021-03"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neural-tube defects (NTDs) are one type of the most serious birth defects. Studies have shown that inositol deficiency is closely related to the occurrence of NTDs. Bone morphogenetic protein (BMP)-mediated Smad signaling pathways have been implicated in neurogenesis and neural-tube closure. However, the role of the BMP\/Smad pathway in inositol-deficiency-induced NTDs remains unclear. Inositol-deficiency models in C57 mice and mouse neural stem cells (mNSCs) were induced with Li2CO3 treatment or inositol withdrawal. The role of the BMP\/Smad pathway in the regulation of cell proliferation and the development of NTDs was determined utilizing qRT-PCR, HE staining, Western blot, immunostaining, MTT assay, EdU staining, and flow cytometry. The intraperitoneal injection of Li2CO3 at Embryonic Day 7.5 induced the occurrence of NTDs. The mRNA levels of Bmp2, Bmp4, Smad1, Smad5, Smad8 and Runx2, the phosphorylation of Smad1\/5\/8, and the nuclear translocation of Runx2 were significantly increased in NTD embryonic brain tissues and mNSCs exposed to Li2CO3 or an inositol-free medium, which were suppressed by BMP receptor selective inhibitor LDN-193189. The Li2CO3-induced phosphorylation of Smad1\/5\/8 was inhibited by inositol supplementation. Cell proliferation was significantly promoted by Li2CO3 exposure or the absence of inositol in mNSCs, which was reversed by LDN-193189. These results suggest that the activation of the BMP\/Smad signaling pathway might play an important role in the development of NTDs induced by maternal Li2CO3 exposure via inositol deficiency.<\/jats:p>","DOI":"10.3390\/ijms232314831","type":"journal-article","created":{"date-parts":[[2022,11,30]],"date-time":"2022-11-30T04:58:50Z","timestamp":1669784330000},"page":"14831","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["BMP\/Smad Pathway Is Involved in Lithium Carbonate-Induced Neural-Tube Defects in Mice and Neural Stem Cells"],"prefix":"10.3390","volume":"23","author":[{"given":"Aiyun","family":"Yang","sequence":"first","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shen","family":"Li","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-0826","authenticated-orcid":false,"given":"Xiuwei","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Guan","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingchao","family":"Liang","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4876-323X","authenticated-orcid":false,"given":"Lijiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Environmental & Viral Oncology, College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhua","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1146\/annurev-neuro-062012-170354","article-title":"Neural tube defects","volume":"37","author":"Greene","year":"2014","journal-title":"Annu. 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