Journal article
Drosophila female germline stem cells undergo mitosis without nuclear breakdown
Current biology, Vol.31(7), pp.1450-1462.e3
04/12/2021
DOI: 10.1016/j.cub.2021.01.033
PMCID: PMC8044017
PMID: 33548191
Abstract
Stem cell homeostasis requires nuclear lamina (NL) integrity. In Drosophila germ cells, compromised NL integrity activates the ataxia telangiectasia and Rad3-related (ATR) and checkpoint kinase 2 (Chk2) checkpoint kinases, blocking germ cell differentiation and causing germline stem cell (GSC) loss. Checkpoint activation occurs upon loss of either the NL protein emerin or its partner barrier-to-autointegration factor, two proteins required for nuclear reassembly at the end of mitosis. Here, we examined how mitosis contributes to NL structural defects linked to checkpoint activation. These analyses led to the unexpected discovery that wild-type female GSCs utilize a non-canonical mode of mitosis, one that retains a permeable but intact nuclear envelope and NL. We show that the interphase NL is remodeled during mitosis for insertion of centrosomes that nucleate the mitotic spindle within the confines of the nucleus. We show that depletion or loss of NL components causes mitotic defects, including compromised chromosome segregation associated with altered centrosome positioning and structure. Further, in emerin mutant GSCs, centrosomes remain embedded in the interphase NL. Notably, these embedded centrosomes carry large amounts of pericentriolar material and nucleate astral microtubules, revealing a role for emerin in the regulation of centrosome structure. Epistasis studies demonstrate that defects in centrosome structure are upstream of checkpoint activation, suggesting that these centrosome defects might trigger checkpoint activation and GSC loss. Connections between NL proteins and centrosome function have implications for mechanisms associated with NL dysfunction in other stem cell populations, including NL-associated diseases, such as laminopathies.
Details
- Title: Subtitle
- Drosophila female germline stem cells undergo mitosis without nuclear breakdown
- Creators
- Tingting Duan - University of IowaRebecca Cupp - University of IowaPamela K. Geyer - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Current biology, Vol.31(7), pp.1450-1462.e3
- Publisher
- Elsevier
- DOI
- 10.1016/j.cub.2021.01.033
- PMID
- 33548191
- PMCID
- PMC8044017
- ISSN
- 0960-9822
- eISSN
- 1879-0445
- Number of pages
- 16
- Grant note
- S10 RR025439-01 / NIH SIG grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA GM087341; R01GM987654 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Roy J. Carver Charitable Trust
- Language
- English
- Date published
- 04/12/2021
- Academic Unit
- Obstetrics and Gynecology; Biochemistry and Molecular Biology
- Record Identifier
- 9984288730102771
Metrics
22 Record Views