Drosophila female germline stem cells undergo mitosis without nuclear breakdown

Duan, Tingting; Cupp, Rebecca; Geyer, Pamela

doi:10.1016/j.cub.2021.01.033

Cited by 21 publications

(14 citation statements)

References 104 publications

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“…First, GFP-BAF and progeroid BAF were dispersed in mitosis (Fig. 4 A), even though nuclear breakdown does not occur [ 67 ]. These observations are consistent with phosphorylation-dependent release of BAF from chromatin during mitosis [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

Duan

Srikantha

Amoiroglou

et al. 2023

Cell. Mol. Life Sci.

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Barrier-to-autointegration factor (BAF/BANF) is a nuclear lamina protein essential for nuclear integrity, chromatin structure, and genome stability. Whereas complete loss of BAF causes lethality in multiple organisms, the A12T missense mutation of the BANF1 gene in humans causes a premature aging syndrome, called Néstor-Guillermo Progeria Syndrome (NGPS). Here, we report the first in vivo animal investigation of progeroid BAF, using CRISPR editing to introduce the NGPS mutation into the endogenous Drosophila baf gene. Progeroid BAF adults are born at expected frequencies, demonstrating that this BAF variant retains some function. However, tissue homeostasis is affected, supported by studies of the ovary, a tissue that depends upon BAF for stem cell survival and continuous oocyte production. We find that progeroid BAF causes defects in germline stem cell mitosis that delay anaphase progression and compromise chromosome segregation. We link these defects to decreased recruitment of centromeric proteins of the kinetochore, indicating dysfunction of cenBAF, a localized pool of dephosphorylated BAF produced by Protein Phosphatase PP4. We show that DNA damage increases in progenitor germ cells, which causes germ cell death due to activation of the DNA damage transducer kinase Chk2. Mitotic defects appear widespread, as aberrant chromosome segregation and increased apoptosis occur in another tissue. Together, these data highlight the importance of BAF in establishing centromeric structures critical for mitosis. Further, these studies link defects in cenBAF function to activation of a checkpoint that depletes progenitor reserves critical for tissue homeostasis, aligning with phenotypes of NGPS patients.

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Section: Resultsmentioning

confidence: 99%

Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

Duan

Srikantha

Amoiroglou

et al. 2023

Cell. Mol. Life Sci.

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“…The shape of the GSC spectrosome varies throughout the cell cycle and it can be used as a morphological marker to help distinguish between the GSC Gap 1 (G1), Synthesis (S), Gap 2 (G2) and Mitosis (M) phases ( Ables and Drummond-Barbosa, 2013 ). Female GSCs undergo mitosis without proper nuclear envelope breakdown, as the nuclear lamina remains intact during division, albeit the mitotic nuclear envelope becomes permeable ( Duan et al, 2021 ). Later in oogenesis, the CB spectrosome grows into a branched figure called a fusome, characteristic of differentiating germline cysts ( de Cuevas and Spradling, 1998 ; Ong and Tan, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

“…phases (Ables and Drummond-Barbosa, 2013). Female GSCs undergo mitosis without proper nuclear envelope breakdown, as the nuclear lamina remains intact during division albeit the mitotic nuclear envelope becomes permeable (Duan et al, 2021). Later in oogenesis, the CB spectrosome grows into a branched figure termed fusome, characteristic of differentiating germline cysts (de Cuevas and Spradling, 1998;Ong and Tan, 2010).…”

Section: Introductionmentioning

confidence: 99%

Live imaging of the Drosophila ovarian niche shows spectrosome and centrosome dynamics during asymmetric germline stem cell division

et al. 2021

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Drosophila female germline stem cells (GSCs) are found inside the cellular niche at the tip of the ovary. They undergo asymmetric divisions to renew the stem cell lineage and to produce sibling cystoblasts that will in turn enter differentiation. GSCs and cystoblasts contain spectrosomes, membranous structures essential to orientate the mitotic spindle and that, particularly in GSCs, change shape depending on the cell cycle phase. Using live imaging and a GFP fusion of the spectrosome component Par-1, we follow the complete spectrosome cycle throughout GSC division and quantify the relative duration of the different spectrosome shapes. We also determine that the Par-1 kinase shuttles between the spectrosome and the cytoplasm during mitosis and observe the continuous addition of new material to the GSC and cystoblast spectrosomes. Next, we utilise the Fly-FUCCI tool to define in live and fixed tissues that GSCs have a shorter G1 compared to the G2 phase. The observation of centrosomes in dividing GSCs allowed us to determine that centrosomes separate very early in G1, prior to centriole duplication. Furthermore, we show that the anterior centrosome associates with the spectrosome only during mitosis and that, upon mitotic spindle assembly, it translocates to the cell cortex, where it remains anchored until centrosome separation. Finally, we demonstrate that the asymmetric division of GSCs is not an intrinsic property of these cells, since the spectrosome of GSC-like cells located outside of the niche can divide symmetrically. Thus, GSCs display unique properties during division, a behaviour influenced by the surrounding niche.

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“…Survival of adult stem cells in the female and male germlines depends upon emerin and BAF ( Barton et al 2013 , 2016 ; Duan et al 2021 ). To gain further insights into the mechanism of stem cell loss, we investigated gene expression changes in the ovary resulting from loss of either NL component.…”

Section: Resultsmentioning

confidence: 99%

Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants

Kitzman

Duan

Pufall

et al. 2021

G3 Genes|Genomes|Genetics

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The nuclear lamina (NL) lines the inner nuclear membrane. This extensive protein network organizes chromatin and contributes to the regulation of transcription, DNA replication and repair. Lap2-emerin-MAN1 domain (LEM-D) proteins are key members of the NL, representing proteins that connect the NL to the genome through shared interactions with the chromatin binding protein Barrier-to-autointegration factor (BAF). Functions of the LEM-D protein emerin and BAF are essential during Drosophila melanogaster oogenesis. Indeed, loss of either emerin or BAF blocks germ cell development and causes loss of germline stem cells, defects linked to deformation of NL structure and non-canonical activation of Checkpoint kinase 2 (Chk2). Here, we investigate contributions of emerin and BAF to gene expression in the ovary. Profiling RNAs from emerin and baf mutant ovaries revealed that nearly all baf mis-regulated genes were shared with emerin mutants, defining a set of NL-regulated genes. Strikingly, loss of Chk2 restored expression of most NL-regulated genes, identifying a large class of Chk2-dependent genes (CDGs). Nonetheless, some genes remained mis-expressed upon Chk2 loss, identifying a smaller class of emerin-dependent genes (EDGs). Properties of EDGs suggest a shared role for emerin and BAF in repression of developmental genes. Properties of CDGs demonstrate that Chk2 activation drives global mis-expression of genes in the emerin and baf mutant backgrounds. Notably, CDGs were found up-regulated in lamin-B mutant backgrounds. These observations predict that Chk2 activation might have a general role in gene expression changes found in NL-associated diseases, such as laminopathies.

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Drosophila female germline stem cells undergo mitosis without nuclear breakdown

Cited by 21 publications

References 104 publications

Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

Analysis of a rare progeria variant of Barrier-to-autointegration factor in Drosophila connects centromere function to tissue homeostasis

Live imaging of the Drosophila ovarian niche shows spectrosome and centrosome dynamics during asymmetric germline stem cell division

Checkpoint activation drives global gene expression changes in Drosophila nuclear lamina mutants

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