Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea
Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker’s organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.777836/full |
| _version_ | 1818404501650931712 |
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| author | Vikrant Borse Tejbeer Kaur Ashley Hinton Kevin Ohlemiller Mark E. Warchol |
| author_facet | Vikrant Borse Tejbeer Kaur Ashley Hinton Kevin Ohlemiller Mark E. Warchol |
| author_sort | Vikrant Borse |
| collection | DOAJ |
| description | Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker’s organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5–15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. This study examined the link between developmental cell death in the GER and the recruitment of macrophages into this region. Cell death in the basal GER begins at P5 and enhanced numbers of macrophages were observed at P7. This pattern of macrophage recruitment was unchanged in mice that were genetically deficient for CX3CR1, the receptor for fractalkine (a known macrophage chemoattractant). We found that injection of T3 at P0 and P1 caused GER cell death to begin at P3, and this premature PCD was accompanied by earlier recruitment of macrophages. We further found that depletion of macrophages from the developing cochlea (using CX3CR1DTR/+ mice and treatment with the CSF1R antagonist BLZ945) had no effect on the pattern of GER regression. Together, these findings suggest that macrophages are recruited into the GER region after initiation of developmental PCD, but that they are not essential for GER regression during cochlear remodeling. |
| first_indexed | 2024-12-14T08:41:10Z |
| format | Article |
| id | doaj.art-2f5b31662b274a53ab3358dc41421279 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-14T08:41:10Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-2f5b31662b274a53ab3358dc414212792022-12-21T23:09:18ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-12-01910.3389/fcell.2021.777836777836Programmed Cell Death Recruits Macrophages Into the Developing Mouse CochleaVikrant Borse0Tejbeer Kaur1Ashley Hinton2Kevin Ohlemiller3Mark E. Warchol4Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, United StatesDepartment of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United StatesDepartment of Otolaryngology, Washington University School of Medicine, St. Louis, MO, United StatesProgrammed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker’s organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5–15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. This study examined the link between developmental cell death in the GER and the recruitment of macrophages into this region. Cell death in the basal GER begins at P5 and enhanced numbers of macrophages were observed at P7. This pattern of macrophage recruitment was unchanged in mice that were genetically deficient for CX3CR1, the receptor for fractalkine (a known macrophage chemoattractant). We found that injection of T3 at P0 and P1 caused GER cell death to begin at P3, and this premature PCD was accompanied by earlier recruitment of macrophages. We further found that depletion of macrophages from the developing cochlea (using CX3CR1DTR/+ mice and treatment with the CSF1R antagonist BLZ945) had no effect on the pattern of GER regression. Together, these findings suggest that macrophages are recruited into the GER region after initiation of developmental PCD, but that they are not essential for GER regression during cochlear remodeling.https://www.frontiersin.org/articles/10.3389/fcell.2021.777836/fullcochleadevelopmentGERcell deathmacrophagethyroid hormone |
| spellingShingle | Vikrant Borse Tejbeer Kaur Ashley Hinton Kevin Ohlemiller Mark E. Warchol Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea Frontiers in Cell and Developmental Biology cochlea development GER cell death macrophage thyroid hormone |
| title | Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea |
| title_full | Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea |
| title_fullStr | Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea |
| title_full_unstemmed | Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea |
| title_short | Programmed Cell Death Recruits Macrophages Into the Developing Mouse Cochlea |
| title_sort | programmed cell death recruits macrophages into the developing mouse cochlea |
| topic | cochlea development GER cell death macrophage thyroid hormone |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.777836/full |
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