MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode
Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation, leading to microphthalmia; therefore, Mab21l1-null mi...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2021-12-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/14/12/dmm049251 |
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| author | Ryuichi Yamada Akira Oguri Katsunori Fujiki Katsuhiko Shirahige Yoshikazu Hirate Masami Kanai-Azuma Hirotaka Takezoe Yoshihiro Akimoto Naoki Takahashi Yoshiakira Kanai |
| author_facet | Ryuichi Yamada Akira Oguri Katsunori Fujiki Katsuhiko Shirahige Yoshikazu Hirate Masami Kanai-Azuma Hirotaka Takezoe Yoshihiro Akimoto Naoki Takahashi Yoshiakira Kanai |
| author_sort | Ryuichi Yamada |
| collection | DOAJ |
| description | Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation, leading to microphthalmia; therefore, Mab21l1-null mice are used as a mouse model for COFG syndrome. In this study, we investigated the early-onset single-cell-level phenotypes of murine Mab21l1-null lens ectoderms using electron microscopy and single-cell RNA sequencing (scRNA-seq). Electron microscopy and immunohistochemical analyses indicated endoplasmic reticulum stress at the 24- to 26-somite stage in Mab21l1-null lens placodes. scRNA-seq analysis revealed that 131 genes were downregulated and 148 were upregulated in Mab21l1-null lens ectoderms relative to the wild type. We successfully identified 21 lens-specific genes that were downregulated in Mab21l1-null cells, including three key genes involved in lens formation: Pitx3, Maf and Sfrp2. Moreover, gene ontology analysis of the 279 differentially expressed genes indicated enrichment in housekeeping genes associated with DNA/nucleotide metabolism prior to cell death. These findings suggest that MAB21L1 acts as a nuclear factor that modulates not only lens-specific gene expression but also DNA/nucleotide metabolic processes during lens placode formation. |
| first_indexed | 2024-12-18T05:34:40Z |
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| id | doaj.art-beecd9a2524d4386b477fed048854f1e |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-18T05:34:40Z |
| publishDate | 2021-12-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-beecd9a2524d4386b477fed048854f1e2022-12-21T21:19:20ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112021-12-01141210.1242/dmm.049251049251MAB21L1 modulates gene expression and DNA metabolic processes in the lens placodeRyuichi Yamada0Akira Oguri1Katsunori Fujiki2Katsuhiko Shirahige3Yoshikazu Hirate4Masami Kanai-Azuma5Hirotaka Takezoe6Yoshihiro Akimoto7Naoki Takahashi8Yoshiakira Kanai9 Department of Veterinary Anatomy, the University of Tokyo, Tokyo 113-8657, Japan Department of Applied Biological Chemistry, the University of Tokyo, Tokyo 113-8657, Japan Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, the University of Tokyo, Tokyo 113-0032, Japan Laboratory of Genome Structure and Function, Institute for Quantitative Biosciences, the University of Tokyo, Tokyo 113-0032, Japan Department of Experimental Animal Model for Human Disease, Center for Experimental Animals, Tokyo Medical and Dental University, Tokyo 113-8510, Japan Department of Experimental Animal Model for Human Disease, Center for Experimental Animals, Tokyo Medical and Dental University, Tokyo 113-8510, Japan Genble Inc., Fukuoka 814-0001, Japan Department of Anatomy, Kyorin University School of Medicine, Tokyo 181-8611, Japan Department of Applied Biological Chemistry, the University of Tokyo, Tokyo 113-8657, Japan Department of Veterinary Anatomy, the University of Tokyo, Tokyo 113-8657, Japan Mutations in human MAB21L1 cause aberrations in lens ectoderm morphogenesis and lead to congenital cerebellar, ocular, craniofacial and genital (COFG) syndrome. Murine Mab21l1-null mutations cause severe cell-autonomous defects in lens formation, leading to microphthalmia; therefore, Mab21l1-null mice are used as a mouse model for COFG syndrome. In this study, we investigated the early-onset single-cell-level phenotypes of murine Mab21l1-null lens ectoderms using electron microscopy and single-cell RNA sequencing (scRNA-seq). Electron microscopy and immunohistochemical analyses indicated endoplasmic reticulum stress at the 24- to 26-somite stage in Mab21l1-null lens placodes. scRNA-seq analysis revealed that 131 genes were downregulated and 148 were upregulated in Mab21l1-null lens ectoderms relative to the wild type. We successfully identified 21 lens-specific genes that were downregulated in Mab21l1-null cells, including three key genes involved in lens formation: Pitx3, Maf and Sfrp2. Moreover, gene ontology analysis of the 279 differentially expressed genes indicated enrichment in housekeeping genes associated with DNA/nucleotide metabolism prior to cell death. These findings suggest that MAB21L1 acts as a nuclear factor that modulates not only lens-specific gene expression but also DNA/nucleotide metabolic processes during lens placode formation.http://dmm.biologists.org/content/14/12/dmm049251mab21l1lens placodescrna-seqtransmission electron microscopy |
| spellingShingle | Ryuichi Yamada Akira Oguri Katsunori Fujiki Katsuhiko Shirahige Yoshikazu Hirate Masami Kanai-Azuma Hirotaka Takezoe Yoshihiro Akimoto Naoki Takahashi Yoshiakira Kanai MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode Disease Models & Mechanisms mab21l1 lens placode scrna-seq transmission electron microscopy |
| title | MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode |
| title_full | MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode |
| title_fullStr | MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode |
| title_full_unstemmed | MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode |
| title_short | MAB21L1 modulates gene expression and DNA metabolic processes in the lens placode |
| title_sort | mab21l1 modulates gene expression and dna metabolic processes in the lens placode |
| topic | mab21l1 lens placode scrna-seq transmission electron microscopy |
| url | http://dmm.biologists.org/content/14/12/dmm049251 |
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