Impact of ATF6 deletion on the embryonic brain development.
| Title: | Impact of ATF6 deletion on the embryonic brain development. |
|---|---|
| Authors: | Nguyen LD; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Nguyen LH; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Dao DX; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Hattori T; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Takarada-Iemata M; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Ishii H; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Tamatani T; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Kawasaki H; Department of Medical Neuroscience, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan.; Shinmyo Y; Department of Neurophysiology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.; Onoue K; Laboratory for Ultrastructural Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.; Yonemura S; Laboratory for Ultrastructural Research, RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan.; Department of Cell Biology, Tokushima University Graduate School of Medicine, Tokushima, Japan.; Zhang J; Division of Molecular Biology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.; Miyake M; Division of Molecular Biology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.; Oyadomari S; Division of Molecular Biology, Institute of Advanced Medical Sciences, Tokushima University, Tokushima, Japan.; Mori K; Kyoto University Institute for Advanced Study, Kyoto, Japan.; Hori O; Department of Neuroanatomy, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa, Japan. |
| Source: | IScience [iScience] 2025 May 02; Vol. 28 (6), pp. 112569. Date of Electronic Publication: 2025 May 02 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Cell Press Country of Publication: United States NLM ID: 101724038 Publication Model: eCollection Cited Medium: Internet ISSN: 2589-0042 (Electronic) Linking ISSN: 25890042 NLM ISO Abbreviation: iScience Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [Cambridge, MA] : Cell Press, [2018]- |
| Abstract: | Although the unfolded protein response (UPR) is activated during brain development, its roles remain unclear. Here, we report that deletion of activating transcription factor 6 (ATF6), consisting of ATF6α and ATF6β, in the developing brain caused microcephaly and neonatal death in mice. Analysis of Atf6a/Atf6b double conditional knockout (dcKO) brains revealed diverse neuronal phenotypes, such as reduced neurogenesis, increased cell death, impaired cortical layer formation, and axon projection defects. Furthermore, hypervasculature, glial defects, and neuroinflammation were observed in dcKO brains. Notably, hypervasculature was detected at E14.5, when endoplasmic reticulum (ER) stress was morphologically unclear, but the UPR was activated to a greater extent in dcKO brains. Expression profiles revealed reduced levels of molecular chaperones in the ER and enhanced levels of PERK- and IRE1-downstream molecules, including VEGFA, in dcKO brains. Administration of a chemical chaperone 4-phenylbutyric acid partially rescued dcKO mice, suggesting roles of ATF6 for improving proteostasis and for coordinating the UPR.; (© 2025 The Author(s).) |
| Competing Interests: | The authors declare no competing interests. |
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| Contributed Indexing: | Keywords: Cell biology; Developmental biology; Neuroscience |
| Entry Date(s): | Date Created: 20250609 Latest Revision: 20250611 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12143657 |
| DOI: | 10.1016/j.isci.2025.112569 |
| PMID: | 40487428 |
| Database: | MEDLINE |
Journal Article