LIF–IGF Axis Contributes to the Proliferation of Neural Progenitor Cells in Developing Rat Cerebrum

• Published in: International journal of molecular sciences Vol. 23; no. 21; p. 13199
• Main Authors: Takata, Sho, Sakata-Haga, Hiromi, Shimada, Hiroki, Tsukada, Tsuyoshi, Sakai, Daisuke, Shoji, Hiroki, Tomosugi, Mitsuhiro, Nakamura, Yuka, Ishigaki, Yasuhito, Iizuka, Hideaki, Hayashi, Yasuhiko, Hatta, Toshihisa
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 30-10-2022; MDPI
• Subjects: Animal models; Autocrine signalling; Cell proliferation; Cells (biology); Cerebrospinal fluid; Cerebrum; DNA chips; DNA microarrays; Fetuses; Gene expression; Growth factors; Immune response; Insulin; insulin-like growth factor 1; insulin-like growth factor 2; Insulin-like growth factor I; Insulin-like growth factors; Leukemia; Leukemia inhibitory factor; Localization; Mental disorders; neural progenitor cell; Neural stem cells; Neurogenesis; Paracrine signalling; Physiological effects; Physiology; Progenitor cells; Ventricle
• DOI: 10.3390/ijms232113199
• EISSN: 1422-0067
• ISSN: 1422-0067; 1661-6596

In rodent models, leukemia inhibitory factor (LIF) is involved in cerebral development via the placenta, and maternal immune activation is linked to psychiatric disorders in the child. However, whether LIF acts directly on neural progenitor cells (NPCs) remains unclear. This study performed DNA microarray analysis and quantitative RT-PCR on the fetal cerebrum after maternal intraperitoneal or fetal intracerebral ventricular injection of LIF at day 14.5 (E14.5) and determined that the expression of insulin-like growth factors (IGF)-1 and -2 was induced by LIF. Physiological IGF-1 and IGF-2 levels in fetal cerebrospinal fluid (CSF) increased from E15.5 to E17.5, following the physiological surge of LIF levels in CSF at E15.5. Immunostaining showed that IGF-1 was expressed in the cerebrum at E15.5 to E19.5 and IGF-2 at E15.5 to E17.5 and that IGF-1 receptor and insulin receptor were co-expressed in NPCs. Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF–IGF axis in cerebral cortical development in an autocrine/paracrine manner.