Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells.
Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away f...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Biology |
| Online Access: | http://europepmc.org/articles/PMC3389017?pdf=render |
| _version_ | 1818620243520520192 |
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| author | Wen Lu M Olivia Casanueva Anthony P Mahowald Mihoko Kato David Lauterbach Edwin L Ferguson |
| author_facet | Wen Lu M Olivia Casanueva Anthony P Mahowald Mihoko Kato David Lauterbach Edwin L Ferguson |
| author_sort | Wen Lu |
| collection | DOAJ |
| description | Drosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division.Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented.Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis. |
| first_indexed | 2024-12-16T17:50:17Z |
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| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T17:50:17Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Biology |
| spelling | doaj.art-3f762b5e2fb8443aaad7a090bdce50002022-12-21T22:22:20ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852012-01-01107e100135710.1371/journal.pbio.1001357Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells.Wen LuM Olivia CasanuevaAnthony P MahowaldMihoko KatoDavid LauterbachEdwin L FergusonDrosophila female germline stem cells (GSCs) reside adjacent to a cellular niche that secretes Bone Morphogenetic Protein (BMP) ligands and anchors the GSCs through adherens junctions. The GSCs divide asymmetrically such that one daughter remains in the niche as a GSC, while the other is born away from the niche and differentiates. However, given that the BMP signal can be diffusible, it remains unclear how a local extracellular asymmetry is sufficient to result in a robust pattern of asymmetric division.Here we show that GSCs are polarized with respect to the cellular niche. We first use a modified biosensor to demonstrate that the small GTPase Rac is asymmetrically activated within the GSC at the niche-GSC interface. Experiments using loss-of-function and gain-of-function mutations in Rac indicate that asymmetric Rac activity both localizes the microtubule binding protein Apc2 to orient one GSC centrosome at the niche-GSC interface during interphase and activates the Jun N-terminal kinase pathway to increase the ability of the GSC to respond to BMP ligands. Other processes act in concert with each function of Rac. Specifically, we demonstrate that the GSC cell cycle arrests at prometaphase if centrosomes are misoriented.Thus, the GSCs, an adult stem cell present in a cellular niche, have a niche-associated polarity that couples control of the division plane with increased response to an extracellular maintenance signal. Other processes work in parallel with the Rac-mediated polarity to ensure a robust pattern of asymmetric division. We suggest that all adult stem cells likely employ multiple, independently acting mechanisms to ensure asymmetric division to maintain tissue homeostasis.http://europepmc.org/articles/PMC3389017?pdf=render |
| spellingShingle | Wen Lu M Olivia Casanueva Anthony P Mahowald Mihoko Kato David Lauterbach Edwin L Ferguson Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. PLoS Biology |
| title | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| title_full | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| title_fullStr | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| title_full_unstemmed | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| title_short | Niche-associated activation of rac promotes the asymmetric division of Drosophila female germline stem cells. |
| title_sort | niche associated activation of rac promotes the asymmetric division of drosophila female germline stem cells |
| url | http://europepmc.org/articles/PMC3389017?pdf=render |
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