Biology subjects

Roach, T. V.

Publications and source records attributed to Roach, T. V..

3 recordsLinked to original sources

bioRxiv2024

Conversion of somatic sex identity in the testis induces female-specific cellular behaviors in the soma and early oocyte specification in the germline

Establishment and maintenance of cellular sex identity is essential for reproduction. Critically, the sex identity of somatic and germline cells must correspond for sperm or oocytes to be produced, with mismatched identity causing infertility in all organisms from flies to humans. In the Drosophila testis, Chronologically inappropriate morphogenesis (Chinmo) is required for maintenance of adult male somatic identity. Loss of chinmo leads to progressive feminization of the male soma, including adoption of female-specific cell morphologies, tissue organization and gene expression. However, the degree to which this feminized soma in the male engages female-specific cellular behaviors or influences the associated XY germline is unknown. Using extended live imaging, we have visualized the process of male-to-female somatic sex conversion upon chinmo loss of function. We find that feminized soma in the testis engage cell behaviors characteristic of ovarian follicle cells (FCs), including female-specific incomplete cytokinesis, as early as one day of chinmo inhibition. In the ovary, FCs collectively migrate around the underlying germ cells to establish the elongated shape of the oocyte. Surprisingly, we find that FC-like soma in chinmo-depleted testes also engage this female-specific collective cell migration. Critically, migration of FC-like cells in the testis has the same molecular requirements as FC migration in the ovary. Depletion of the basement membrane protein Perlecan or adhesion protein Ecadherin significantly disrupts rotational migration in both the ovary and chinmo-depleted testes. Finally, we find that feminized soma non-autonomously alters sex identity of the associated XY germ cells, inducing expression of a protein required for early oocyte specification. Taken together, our work reveals a dramatic transformation of somatic cell behavior during the process of sex conversion and provides a powerful model to study soma-derived induction of oocyte identity.

developmental biology↗

bioRxiv2023

Mating induces ecdysone signaling in the Drosophila testis niche disrupting somatic encystment of germ cells and stem cell cytokinesis

Germline maintenance relies on adult stem cells to continually replenish lost gametes over a lifetime and respond to external cues altering the demands on the tissue. Mating worsens germline homeostasis over time, yet a negative impact on stem cell behavior has not been explored. Using extended live imaging of the Drosophila testis stem cell niche, we find that short periods of mating in young males disrupts cytokinesis in germline stem cells (GSCs). This defect leads to failure of abscission, preventing release of differentiating cells from the niche. We find that GSC abscission failure is caused by increased ecdysone hormone signaling induced upon mating, which leads to disrupted somatic encystment of the germline. Abscission failure is rescued by isolating males from females but recurs with resumption of mating. Importantly, reiterative mating also leads to increased GSC loss, requiring increased restoration of stem cells via symmetric renewal and de-differentiation. Together, these results suggest a model whereby acute mating results in hormonal changes that negatively impact GSC cytokinesis but preserves the stem cell population. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/562562v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@193d2f7org.highwire.dtl.DTLVardef@1ff602borg.highwire.dtl.DTLVardef@102cf0eorg.highwire.dtl.DTLVardef@167bd5f_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2020

Transcriptome analysis uncovers distinct modes of epigenetic gene changes in early versus late stages of amyloid-β induced Alzheimer's disease pathology

Alzheimers disease (AD) is an age-related neurodegenerative disorder hallmarked by amyloid-{beta} (A{beta}) plaque accumulation, neuronal cell death, and cognitive deficits that worsen during disease progression. Histone acetylation dysregulation, caused by an imbalance between reduced histone acetyltransferases (HAT) Tip60 and increased histone deacetylase 2 (HDAC2) levels, can directly contribute to AD pathology. However, whether such AD-associated neuroepigenetic alterations occur in response to A{beta} peptide production and can be protected against by increasing Tip60 levels over the course of neurodegenerative progression remains unknown. Here we profile Tip60 HAT/HDAC2 dynamics and transcriptome-wide changes across early and late stage AD pathology in the Drosophila brain produced solely by human amyloid-{beta}42. We show that early A{beta}42 induction leads to disruption of Tip60 HAT/HDAC2 balance during early neurodegenerative stages preceding A{beta} plaque accumulation that persists into late AD stages. Correlative transcriptome-wide studies reveal alterations in biological processes we classified as transient (early-stage only), late-onset (late-stage only), and constant (both). Increasing Tip60 HAT levels in the A{beta}42 fly brain protects against AD functional pathologies that include A{beta} plaque accumulation, neural cell death, cognitive deficits, and shorter life-span. Strikingly, Tip60 protects against A{beta}42-induced transcriptomic alterations via distinct mechanisms during early and late stages of neurodegeneration. Our findings reveal distinct modes of neuroepigenetic gene changes and Tip60 neuroprotection in early versus late stages in AD that can serve as early biomarkers for AD, and support the therapeutic potential of Tip60 over the course of AD progression.

neuroscience↗