PMID- 31147466 OWN - NLM STAT- MEDLINE DCOM- 20200406 LR - 20200408 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 116 IP - 25 DP - 2019 Jun 18 TI - ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain. PG - 12494-12499 LID - 10.1073/pnas.1901067116 [doi] AB - Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca(2+)-activated chloride channel, mediates the Ca(2+)-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain. CI - Copyright (c) 2019 the Author(s). Published by PNAS. FAU - Hong, Gyu-Sang AU - Hong GS AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Lee, Sung Hoon AU - Lee SH AD - College of Pharmacy, Chung-ang University, 06974 Seoul, Korea. FAU - Lee, Byeongjun AU - Lee B AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Choi, Jae Hyouk AU - Choi JH AD - Division of Bio-Medical Science and Technology, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Oh, Soo-Jin AU - Oh SJ AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Jang, Yongwoo AU - Jang Y AD - Department of Biomedical Engineering, Hanyang University, 04763 Seoul, Korea. FAU - Hwang, Eun Mi AU - Hwang EM AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. AD - Division of Bio-Medical Science and Technology, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Kim, Hyungsup AU - Kim H AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Jung, Jooyoung AU - Jung J AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea. FAU - Kim, In-Beom AU - Kim IB AD - Department of Anatomy, College of Medicine, Catholic University, 06591 Seoul, Korea. FAU - Oh, Uhtaek AU - Oh U AUID- ORCID: 0000-0002-8935-8863 AD - Brain Science Institute, Korea Institute of Science and Technology, 02792 Seoul, Korea; utoh@kist.re.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190530 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (ANO1 protein, mouse) RN - 0 (Anoctamin-1) RN - 0 (Bdnf protein, mouse) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Chlorides) SB - IM MH - Animals MH - Anoctamin-1/genetics/*physiology MH - Brain/*cytology/*embryology/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Chlorides/metabolism MH - Down-Regulation MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neuroglia/*cytology/metabolism MH - Up-Regulation PMC - PMC6589654 OTO - NOTNLM OT - Anoctamin 1 OT - TMEM16A OT - cortical development OT - neural stem cell OT - radial glial cell COIS- The authors declare no conflict of interest. EDAT- 2019/05/31 06:00 MHDA- 2020/04/09 06:00 PMCR- 2019/05/30 CRDT- 2019/06/01 06:00 PHST- 2019/05/31 06:00 [pubmed] PHST- 2020/04/09 06:00 [medline] PHST- 2019/06/01 06:00 [entrez] PHST- 2019/05/30 00:00 [pmc-release] AID - 1901067116 [pii] AID - 201901067 [pii] AID - 10.1073/pnas.1901067116 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2019 Jun 18;116(25):12494-12499. doi: 10.1073/pnas.1901067116. Epub 2019 May 30.