PMID- 28687747 OWN - NLM STAT- MEDLINE DCOM- 20190110 LR - 20231213 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Jul 7 TI - Lamin B1 levels modulate differentiation into neurons during embryonic corticogenesis. PG - 4897 LID - 10.1038/s41598-017-05078-6 [doi] LID - 4897 AB - Lamin B1, a key component of the nuclear lamina, plays an important role in brain development. Ablation of endogenous Lamin B1 (Lmnb1) in the mouse strongly impairs embryonic brain development and corticogenesis. However, the mechanisms underlying these neurodevelopmental effects are unknown. Here, we report that Lamin B1 levels modulate the differentiation of murine neural stem cells (NSCs) into neurons and astroglial-like cells. In vitro, endogenous Lmnb1 depletion favors NSC differentiation into glial fibrillar acidic protein (GFAP)-immunoreactive cells over neurons, while overexpression of human Lamin B1 (LMNB1) increases the proportion of neurons. In Lmnb1-null embryos, neurogenesis is reduced, while in vivo Lmnb1 silencing in mouse embryonic brain by in utero electroporation of a specific Lmnb1 sh-RNA results in aberrant cortical positioning of neurons and increased expression of the astrocytic marker GFAP in the cortex of 7-day old pups. Together, these results indicate that finely tuned levels of Lamin B1 are required for NSC differentiation into neurons, proper expression of the astrocytic marker GFAP and corticogenesis. FAU - Mahajani, Sameehan AU - Mahajani S AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. AD - Universitaetsmedizin Goettingen, Waldweg 33, Goettingen, 37073, Germany. FAU - Giacomini, Caterina AU - Giacomini C AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. AD - Division of Cancer Studies, King's College London, New Hunt's House, Guy's Campus, London, SE1 1UL, UK. FAU - Marinaro, Federica AU - Marinaro F AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. FAU - De Pietri Tonelli, Davide AU - De Pietri Tonelli D AUID- ORCID: 0000-0001-9537-8900 AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. FAU - Contestabile, Andrea AU - Contestabile A AUID- ORCID: 0000-0002-5417-4722 AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. FAU - Gasparini, Laura AU - Gasparini L AD - Dept. of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Genova, Italy. laura.gasparini@abbvie.com. AD - Abbvie Deutschland GmbH & Co, Knollstr, Ludwigshafen, 67061, Germany. laura.gasparini@abbvie.com. LA - eng GR - U42 OD012210/OD/NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170707 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Lamin Type B) RN - 0 (RNA, Small Interfering) RN - 0 (glial fibrillary astrocytic protein, mouse) SB - IM MH - Animals MH - Animals, Newborn MH - Astrocytes/cytology/*metabolism MH - Cell Differentiation MH - Cerebral Cortex/cytology/growth & development/*metabolism MH - Embryo, Mammalian MH - Female MH - Gene Expression Regulation, Developmental MH - Glial Fibrillary Acidic Protein/*genetics/metabolism MH - Lamin Type B/antagonists & inhibitors/*genetics/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Neural Stem Cells/cytology/metabolism MH - Neurogenesis/*genetics MH - Neurons/cytology/*metabolism MH - Pregnancy MH - RNA, Small Interfering/genetics/metabolism MH - Signal Transduction PMC - PMC5501862 COIS- The authors declare that they have no competing interests. EDAT- 2017/07/09 06:00 MHDA- 2019/01/11 06:00 PMCR- 2017/07/07 CRDT- 2017/07/09 06:00 PHST- 2016/12/09 00:00 [received] PHST- 2017/05/24 00:00 [accepted] PHST- 2017/07/09 06:00 [entrez] PHST- 2017/07/09 06:00 [pubmed] PHST- 2019/01/11 06:00 [medline] PHST- 2017/07/07 00:00 [pmc-release] AID - 10.1038/s41598-017-05078-6 [pii] AID - 5078 [pii] AID - 10.1038/s41598-017-05078-6 [doi] PST - epublish SO - Sci Rep. 2017 Jul 7;7(1):4897. doi: 10.1038/s41598-017-05078-6.