Biology subjects

Ables, E. T.

Publications and source records attributed to Ables, E. T..

5 recordsLinked to original sources

bioRxiv2025

Ecdysone Receptor autonomously controls germ cell differentiation in the Drosophila ovary

In the Drosophila ovary, the steroid hormone ecdysone controls germline stem cell (GSC) maintenance and germ cell differentiation. Prior studies demonstrated that ecdysone regulates germ cell differentiation non-autonomously via the nuclear receptor Ecdysone Receptor (EcR) in ovarian somatic cells. Although EcR is also expressed in GSCs and their differentiating daughters, potential direct roles for EcR in GSCs independent of the soma have not been examined. Here, we demonstrate that EcR functions autonomously in GSCs and cystoblasts to control germline differentiation. While depletion of EcR from GSCs mildly reduces GSC self-renewal, over-expression of EcR specifically in GSCs and cystoblasts impedes germ cell differentiation, phenotypically resembling bag of marbles loss-of-function and Bone Morphogenetic Protein signaling constitutive activation. We propose that while low levels of EcR are essential to maintain GSC self-renewal and permit initial differentiation, higher levels of EcR accumulate in differentiated germ cells to promote transcription of maternal genes, providing temporal control over germline differentiation. These data support the model that stem cells harbor unique mechanisms to integrate signals from multiple cell sources that safeguard their self-renewal in response to local and physiological cues. SUMMARY STATEMENTThe nuclear receptor EcR modulates stem cell maintenance and differentiation in ovarian germ cells.

developmental biology↗

bioRxiv2025

Fusome morphogenesis is sufficient to promote female germline stem cell self-renewal in Drosophila

Germline cysts, or interconnected groups of germ cells, promote the synchronization of gamete development in vertebrates and invertebrates. In the Drosophila ovary, cyst formation is coordinated by the fusome, a unique endoplasmic reticulum-like organelle. Although many structural components of the fusome have been characterized, little is known about the genetic factors that control fusome growth and distribution between germ cells. Here, we identify the {beta}-importin, Tnpo-SR, as an important regulator of fusome morphogenesis in germline stem cells (GSCs) and their dividing daughters. Although Tnpo-SR does not aggregate at fusomes or centrosomes, Tnpo-SR null mutants fail to form proper fusomes and knock-down of Tnpo-SR reduces fusome accumulation, ultimately leading to cyst fragmentation and improper numbers of germ cells within an egg chamber. Tnpo-SR depletion disrupts microtubule organization during interphase and sub-cellular localization of the microtubule associated protein Asp. However, overexpression of asp is not sufficient to restore fusome size or cyst architecture when Tnpo-SR is depleted, suggesting that Tnpo-SR-dependent regulation of asp does not solely control fusome morphogenesis. Instead, we find that restoring fusome size by overexpressing the core fusome component hu-li tai shao or the polarity factor Par3/bazooka is sufficient to restore fusome area in Tnpo-SR-depleted GSCs. Moreover, restoration of fusome area in the absence of Tnpo-SR also rescues cyst organization and oocyte specification, suggesting that Tnpo-SR functions upstream of fusome structural component production. Taken together, these data functionally link nuclear import/export machinery to fusome morphogenesis during Drosophila germline cyst development. ARTICLE SUMMARYThe fusome plays a key role in cyst formation in the Drosophila ovarian germline, yet regulation of fusome growth and distribution between germ cells after mitosis remains understudied. Through loss-of-function analyses, the authors identify Tnpo-SR as a novel regulator of fusome morphogenesis. Tnpo-SR depletion reduces the core fusome structural component Hts in germline stem cells (GSCs) and disrupts microtubule organization and nucleation. Overexpression of Hts or Par3/bazooka in Tnpo-SR-depleted GSCs restores fusome size, which in turn rescues cyst organization and oocyte specification. These findings establish Tnpo-SR as an upstream regulator of Hts during fusome morphogenesis.

developmental biology↗

bioRxiv2024

Analysis of a hypomorphic mei-P26 mutation reveals developmental control of CO patterning mechanisms

Female gametogenesis in Drosophila requires differentiation and mitotic division of germ cells, acquisition of oocyte fate, and entry into meiosis. Each of these processes is well understood individually; however, little is known about the mechanisms that ensure proper temporal integration of germ cell differentiation and meiotic chromosome dynamics. Here, we take advantage of a hypomorphic mutation in mei-P26, a well-characterized gene with multiple diverse functions in germ cell development, to determine the consequences of disrupting the coordination between development and meiosis. While null mutations in mei-P26 lead to tumorous ovaries, the hypomorphic allele mei-P261 allows sufficient germ cell differentiation and fertility to support analysis of meiotic chromosome dynamics. Unlike wildtype germaria, 60% of cysts in mei-P261 germaria co-express the differentiation factor Bag of marbles (Bam) and the oocyte specification factor Orb, suggesting that mitotic division is delayed. In this context, the synaptonemal complex rarely assembles into full length continuous tracks and instead is missing or present only as foci. Despite these phenotypes, meiotic double-strand breaks still form and are repaired as crossovers, but the crossovers are mis-patterned and form in centromere proximal regions rather than chromosome arms. The strength of crossover interference is significantly reduced and the centromere effect is lost, but crossover assurance is intact and the meiosis-specific machinery is used to form crossovers. We suggest a model where the failure to exit mitosis in a timely fashion causes cells to enter meiosis while still receiving mitotic signals, resulting in abnormal meiotic chromosome dynamics and impaired crossover formation. Article summaryFemale gametogenesis in Drosophila requires the precise temporal integration of germ cell differentiation and meiotic entry. Using a hypomorphic mutation in mei-P26, we investigated how disrupting this coordination affects meiotic chromosome dynamics. In mei-P261 mutants, delayed mitotic exit causes cells to enter meiosis while still receiving mitotic signals. This results in fragmented synaptonemal complex and the loss of some but not all CO patterning mechanisms. These results suggest that timely mitotic exit is critical for establishing the proper regulatory landscape required for meiotic recombination.

genetics↗

bioRxiv2021

β-importins Tnpo-SR and Cadmus and the small GTPase Ran promote ovarian cyst formation in Drosophila

Germ cells undergo mitotic expansion via incomplete cytokinesis, forming cysts of undifferentiated cells that remain interconnected prior to meiotic initiation, through mechanisms that are not well-defined. In somatic cells, Ras-related nuclear protein (Ran) spatiotemporally regulates mitotic spindle assembly, cleavage furrow formation and abscission. Here, we identify Ran and {beta}-importins as critical regulators of cyst development in the Drosophila ovary. Depletion of Ran or the {beta}-importins Tnpo-SR and cadmus disrupts oocyte selection and results in egg chambers with variable numbers of germ cells, suggesting abnormal cyst development and cyst fragmentation. We demonstrate that Ran, Tnpo-SR, and Cadmus regulate key cellular processes during cyst formation, including cell cycle dynamics, fusome biogenesis, and ring canal stability, yet do so independently of mitotic spindle assembly. Further, Tnpo-SR and Cadmus control cyclin accumulation and suppress cytokinesis independent of Ran-GTP, suggesting that {beta}-importins sequester protein cargos that normally promote the mitotic-to-meiotic transition. Our data demonstrates that Ran and {beta}-importins are critical for germ cell cyst formation, a role that is likely conserved in other organisms. SUMMARY STATEMENTRan and two {beta}-importins function coordinately to promote oocyte selection and cyst development in the Drosophila ovary.

developmental biology↗

bioRxiv2018

Multifunctional RNA-binding proteins mediate ecdysone-dependent germline stem cell self-renewal in Drosophila

Steroid hormones promote stem cell self-renewal in many tissues; however, the molecular mechanisms by which hormone signaling is integrated with niche-derived signals are largely uncharacterized. In the Drosophila ovary, the steroid hormone ecdysone promotes germline stem cell (GSC) self-renewal. Despite strong evidence that ecdysone modulates the reception of bone morphogenetic protein (BMP) signals in GSCs, transcriptional targets of ecdysone signaling that facilitate BMP reception are unknown. Here, we report that ecdysone signaling promotes the expression of the heterogeneous nuclear ribonucleoproteins (hnRNPs) squid, hephaestus, Hrb27C, and Hrb87F in GSCs. These hnRNPs functionally interact with ecdysone signaling to control GSC number and are cell autonomously required in GSCs for their maintenance. We demonstrate that hnRNPs promote GSC self-renewal by binding to transcripts essential for proper BMP signaling, including the BMP receptors thickveins and punt. Our findings support the model that stem cells coordinate local and long-range signals at the transcriptional and post-transcriptional levels to maintain self-renewal in response to physiological demand. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=157 SRC="FIGDIR/small/321109v2_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@1ef6228org.highwire.dtl.DTLVardef@1156460org.highwire.dtl.DTLVardef@170ff15org.highwire.dtl.DTLVardef@17ae36b_HPS_FORMAT_FIGEXP M_FIG GRAPHICAL ABSTRACTEcdysone signaling regulates distinct hnRNPs that bind to BMP signaling targets to control GSC self-renewal. C_FIG SUMMARY STATEMENTEcdysone signaling promotes expression of heterogeneous ribonucleoproteins that modulate BMP-dependent germline stem cell self-renewal in the Drosophila ovary.

developmental biology↗