{"abstract":[{"text":"In the developing vertebrate central nervous system, neurons and glia typically arise sequentially from common progenitors. Here, we report that the transcription factor Forkhead Box G1 (Foxg1) regulates gliogenesis in the mouse neocortex via distinct cell-autonomous roles in progenitors and in postmitotic neurons that regulate different aspects of the gliogenic FGF signalling pathway. We demonstrate that loss of Foxg1 in cortical progenitors at neurogenic stages causes premature astrogliogenesis. We identify a novel FOXG1 target, the pro-gliogenic FGF pathway component Fgfr3, which is suppressed by FOXG1 cell-autonomously to maintain neurogenesis. Furthermore, FOXG1 can also suppress premature astrogliogenesis triggered by the augmentation of FGF signalling. We identify a second novel function of FOXG1 in regulating the expression of gliogenic ligand FGF18 in new born neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons increases Fgf18 expression and enhances gliogenesis in the progenitors. These results fit well with the model that new born neurons secrete cues that trigger progenitors to produce the next wave of cell types, astrocytes. If FGF signalling is attenuated in Foxg1 null progenitors, they progress to oligodendrocyte production. Therefore, loss of FOXG1 transitions the progenitor to a gliogenic state, producing either astrocytes or oligodendrocytes depending on FGF signalling levels. Our results uncover how FOXG1 integrates extrinsic signalling via the FGF pathway to regulate the sequential generation of neurons, astrocytes, and oligodendrocytes in the cerebral cortex.","lang":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1101/2023.11.30.569337","open_access":"1"}],"_id":"14647","department":[{"_id":"SiHi"}],"language":[{"iso":"eng"}],"citation":{"ieee":"M. Bose <i>et al.</i>, “Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","mla":"Bose, Mahima, et al. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2023.11.30.569337\">10.1101/2023.11.30.569337</a>.","short":"M. Bose, V. Suresh, U. Mishra, I. Talwar, A. Yadav, S. Biswas, S. Hippenmeyer, S. Tole, BioRxiv (n.d.).","ama":"Bose M, Suresh V, Mishra U, et al. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2023.11.30.569337\">10.1101/2023.11.30.569337</a>","chicago":"Bose, Mahima, Varun Suresh, Urvi Mishra, Ishita Talwar, Anuradha Yadav, Shiona Biswas, Simon Hippenmeyer, and Shubha Tole. “Dual Role of FOXG1 in Regulating Gliogenesis in the Developing Neocortex via the FGF Signalling Pathway.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2023.11.30.569337\">https://doi.org/10.1101/2023.11.30.569337</a>.","ista":"Bose M, Suresh V, Mishra U, Talwar I, Yadav A, Biswas S, Hippenmeyer S, Tole S. Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. bioRxiv, <a href=\"https://doi.org/10.1101/2023.11.30.569337\">10.1101/2023.11.30.569337</a>.","apa":"Bose, M., Suresh, V., Mishra, U., Talwar, I., Yadav, A., Biswas, S., … Tole, S. (n.d.). Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2023.11.30.569337\">https://doi.org/10.1101/2023.11.30.569337</a>"},"date_published":"2023-12-01T00:00:00Z","publication_status":"submitted","date_updated":"2023-12-11T07:37:17Z","month":"12","article_processing_charge":"No","day":"01","author":[{"full_name":"Bose, Mahima","last_name":"Bose","first_name":"Mahima"},{"last_name":"Suresh","first_name":"Varun","full_name":"Suresh, Varun"},{"full_name":"Mishra, Urvi","first_name":"Urvi","last_name":"Mishra"},{"full_name":"Talwar, Ishita","first_name":"Ishita","last_name":"Talwar"},{"full_name":"Yadav, Anuradha","first_name":"Anuradha","last_name":"Yadav"},{"last_name":"Biswas","first_name":"Shiona","full_name":"Biswas, Shiona"},{"orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","full_name":"Hippenmeyer, Simon","first_name":"Simon","last_name":"Hippenmeyer"},{"full_name":"Tole, Shubha","last_name":"Tole","first_name":"Shubha"}],"publication":"bioRxiv","doi":"10.1101/2023.11.30.569337","type":"preprint","status":"public","acknowledgement":"We thank Dr. Shital Suryavanshi and the animal house staff of the Tata Institute of\r\nFundamental Research (TIFR) for their excellent support; Gord Fishell and Goichi Miyoshi for\r\nthe Foxg1 floxed mouse line; Hiroshi Kawasaki for the plasmids pCAG-FGF8 and pCAGsFGFR3c. We thank Prof. S.K. Lee for the Foxg1lox/lox genotyping primers and protocol. We thank Dr. Deepak Modi and Dr. Vainav Patel for allowing us to use the NIRRCH FACS Facility and the staff of the NIRRCH and TIFR FACS facilities for their assistance.\r\nWe thank Denis Jabaudon for his critical comments on the manuscript and members of the\r\nJabaudon lab for helpful discussions. This work was funded by the Department of Atomic\r\nEnergy (DAE), Govt. of India (Project Identification no. RTI4003, DAE OM no.\r\n1303/2/2019/R&D-II/DAE/2079).","title":"Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway","year":"2023","publisher":"Cold Spring Harbor Laboratory","date_created":"2023-12-06T13:07:01Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","oa":1}