Hif1α-dependent hypoxia signaling contributes to the survival of deep-layer neurons and cortex formation in a mouse model

Molecular Brain

Hiromi Sakata-Haga¹  Toshihisa Hatta¹  Mitsuhiro Tomosugi¹  Hiroko Masuta¹  Daisuke Sakai²  Hiroki Shoji²  Yuki Murakami³  Tomonori Kurokawa⁴  Takeru Sugawara⁴ 

[1] Department of Anatomy, Kanazawa Medical University;Department of Biology, Kanazawa Medical University;Department of Hygiene and Public Health, Kansai Medical University;Department of Medical Life Systems, Doshisha University;

关键词: Hif1α;    Hypoxia;    Cortex;    Telencephalon;    Mouse;   

DOI  :  10.1186/s13041-022-00911-0

来源: DOAJ

【 摘 要 】

Abstract Hypoxia-inducible factor 1 α (Hif1α) plays a crucial role in brain development. To study the function of Hif1α in early brain development, we generated neuroepithelial cell-specific Hif1α-knockout mice. Hif1α-knockout mice died soon after birth; these mice exhibited an abnormal head shape, indicating the presence of brain defects. Morphological analysis revealed that Hif1α ablation reduced the overall size of the brain, especially affecting the telencephalon. Neuronal apoptosis predominantly occurred in deep-layer neurons, consequently the alignment of cortical layers was severely disorganized in Hif1α knockout mice. Furthermore, we demonstrated that Vegf signaling contributes to the survival of deep-layer neurons as a downstream effector of Hif1α-dependent hypoxia signaling. Taken together, our findings demonstrate that Hif1α plays a critical role in the early stages of telencephalon development.

【 授权许可】

Unknown