Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway
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 postmit...
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eLife Sciences Publications Ltd
2025-03-01
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| Online Access: | https://elifesciences.org/articles/101851 |
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| author | Mahima Bose Ishita Talwar Varun Suresh Urvi Mishra Shiona Biswas Anuradha Yadav Shital T Suryavanshi Simon Hippenmeyer Shubha Tole |
| author_facet | Mahima Bose Ishita Talwar Varun Suresh Urvi Mishra Shiona Biswas Anuradha Yadav Shital T Suryavanshi Simon Hippenmeyer Shubha Tole |
| author_sort | Mahima Bose |
| collection | DOAJ |
| description | 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 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 cues in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis in the progenitors via FGF signalling. These results fit well with the model that newborn 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. |
| format | Article |
| id | doaj-art-95f00dc341ee4cfba4f38f4e4b0936a6 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-95f00dc341ee4cfba4f38f4e4b0936a62025-08-20T02:52:59ZengeLife Sciences Publications LtdeLife2050-084X2025-03-011310.7554/eLife.101851Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathwayMahima Bose0https://orcid.org/0000-0002-9069-7889Ishita Talwar1Varun Suresh2https://orcid.org/0000-0002-9177-9843Urvi Mishra3https://orcid.org/0000-0002-2299-7417Shiona Biswas4https://orcid.org/0000-0003-4308-2133Anuradha Yadav5Shital T Suryavanshi6Simon Hippenmeyer7https://orcid.org/0000-0003-2279-1061Shubha Tole8https://orcid.org/0000-0001-6584-443XDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaInstitute of Science and Technology Austria, Klosterneuburg, AustriaDepartment of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, IndiaIn 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 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 cues in newborn neocortical upper-layer neurons. Loss of FOXG1 in postmitotic neurons non-autonomously enhances gliogenesis in the progenitors via FGF signalling. These results fit well with the model that newborn 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.https://elifesciences.org/articles/101851Foxg1neuron-glia cell fategliogenesiscortical development |
| spellingShingle | Mahima Bose Ishita Talwar Varun Suresh Urvi Mishra Shiona Biswas Anuradha Yadav Shital T Suryavanshi Simon Hippenmeyer Shubha Tole Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway eLife Foxg1 neuron-glia cell fate gliogenesis cortical development |
| title | Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway |
| title_full | Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway |
| title_fullStr | Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway |
| title_full_unstemmed | Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway |
| title_short | Dual role of FOXG1 in regulating gliogenesis in the developing neocortex via the FGF signalling pathway |
| title_sort | dual role of foxg1 in regulating gliogenesis in the developing neocortex via the fgf signalling pathway |
| topic | Foxg1 neuron-glia cell fate gliogenesis cortical development |
| url | https://elifesciences.org/articles/101851 |
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