Post-eclosion growth in the Drosophila ejaculatory duct is driven by Juvenile hormone signaling and is essential for male fertility.

The Drosophila Ejaculatory duct (ED) is a secretory tissue of the somatic male reproductive system. The ED is involved in the secretion of seminal fluid components and ED-specific antimicrobial peptides that aid in fertility and the female post-mating response. The ED is composed of secretory epithelial cells surrounded by a layer of innervated contractile muscle.

Cell cycle re-entry in the aging brain.

The brain is an organ comprised mostly of long-lived, quiescent cells that perform vital functions throughout an animal's life. Due to the brain's limited regenerative ability, these long-lived cells must engage unique mechanisms to cope with accumulated damage over time. We have shown that a subset of differentiated neuronal and glial cells in the fruit fly brain become polyploid during adulthood.

Post-eclosion growth in the Ejaculatory Duct is driven by Juvenile Hormone signaling and is essential for male fertility.

The Ejaculatory duct (ED) is a secretory tissue of the somatic male reproductive system. The ED is involved in the secretion of seminal fluid components and ED-specific antimicrobial peptides that aid in fertility and the female post-mating response. The ED is composed of secretory epithelial cells surrounded by a layer of innervated contractile muscle.

Transcriptional repression and enhancer decommissioning silence cell cycle genes in postmitotic tissues.

The mechanisms that maintain a non-cycling status in postmitotic tissues are not well understood. Many cell cycle genes have promoters and enhancers that remain accessible even when cells are terminally differentiated and in a non-cycling state, suggesting their repression must be maintained long term. In contrast, enhancer decommissioning has been observed for rate-limiting cell cycle genes in the Drosophila wing, a tissue where the cells die soon after eclosion, but it has been unclear if this also occurs in other contexts of terminal differentiation.

Oncogenic signaling in the adult prostate-like accessory gland leads to activation of a conserved pro-tumorigenic program, in the absence of proliferation.

models for tumorigenesis and metastasis have revealed conserved mechanisms of signaling that are also involved in mammalian cancer. Many of these models use the proliferating tissues of the larval stages of development, when tissues are highly mitotically active, or stem cells are abundant. Fewer tumorigenesis models use adult animals to initiate tumor formation when many tissues are largely terminally differentiated and postmitotic.

Transcriptional repression and enhancer decommissioning silence cell cycle genes in postmitotic tissues.

The mechanisms that maintain a non-cycling status in postmitotic tissues are not well understood. Many cell cycle genes have promoters and enhancers that remain accessible even when cells are terminally differentiated and in a non-cycling state, suggesting their repression must be maintained long term. In contrast, enhancer decommissioning has been observed for rate-limiting cell cycle genes in the wing, a tissue where the cells die soon after eclosion, but it has been unclear if this also occurs in other contexts of terminal differentiation.

Cell cycle variants during Drosophila male accessory gland development.

The Drosophila melanogaster male accessory gland (AG) is a functional analog of the mammalian prostate and seminal vesicles containing two secretory epithelial cell types, termed main and secondary cells. This tissue is responsible for making and secreting seminal fluid proteins and other molecules that contribute to successful reproduction. The cells of this tissue are binucleate and polyploid, due to variant cell cycles that include endomitosis and endocycling during metamorphosis.

A tissue dissociation method for ATAC-seq and CUT&RUN in pupal tissues.

Chromatin accessibility, histone modifications, and transcription factor binding are highly dynamic during metamorphosis and drive global changes in gene expression as larval tissues differentiate into adult structures. Unfortunately, the presence of pupa cuticle on many tissues during metamorphosis prevents enzyme access to cells and has limited the use of enzymatic in situ methods for assessing chromatin accessibility and histone modifications. Here, we present a dissociation method for cuticle-bound pupal tissues that is compatible for use with ATAC-Seq and CUT&RUN to interrogate chromatin accessibility and histone modifications.

HER2 as a potential therapeutic target on quiescent prostate cancer cells.

Quiescent prostate cancer (PCa) cells are common in tumors but are often resistant to chemotherapy. Quiescent PCa cells are also enriched for a stem-like tumor initiating population, and can lead to recurrence after dormancy. Unfortunately, quiescent PCa cells are difficult to identify and / or target with treatment in part because the relevant markers are intracellular and regulated by protein stability.

Using Mosaic Cell Labeling to Visualize Polyploid Cells in the Drosophila Brain.

Traditional methods used to study endoreplication have limitations when used to identify rare events of polyploidization in complex, densely-packed tissues. Here, we describe a method to identify and visualize polyploid cells in situ using an existing mosaic, multicolor labeling technique named "CoinFLP" (Bosch et al., Development 142(3):597-606, 2015).

Developing Future Biologists: developmental biology for undergraduates from underserved communities.

Developing Future Biologists (DFB) is an inclusive, trainee-run organization that strives to excite and engage the next generation of biologists, regardless of race, gender or socioeconomic status, in the field of developmental biology. DFB offers a week-long course consisting of active lectures, hands-on laboratory sessions, and professional development opportunities through interactions with scientists from a variety of backgrounds and careers. A major goal of DFB is to propel undergraduate students from underserved communities to pursue biomedical research opportunities and advanced degrees in science.

Misregulation of Nucleoporins 98 and 96 leads to defects in protein synthesis that promote hallmarks of tumorigenesis.

Nucleoporin 98KD (Nup98) is a promiscuous translocation partner in hematological malignancies. Most disease models of Nup98 translocations involve ectopic expression of the fusion protein under study, leaving the endogenous Nup98 loci unperturbed. Overlooked in these approaches is the loss of one copy of normal Nup98 in addition to the loss of Nup96 - a second Nucleoporin encoded within the same mRNA and reading frame as Nup98 - in translocations.

Monitoring Spontaneous Quiescence and Asynchronous Proliferation-Quiescence Decisions in Prostate Cancer Cells.

The proliferation-quiescence decision is a dynamic process that remains incompletely understood. Live-cell imaging with fluorescent cell cycle sensors now allows us to visualize the dynamics of cell cycle transitions and has revealed that proliferation-quiescence decisions can be highly heterogeneous, even among clonal cell lines in culture. Under normal culture conditions, cells often spontaneously enter non-cycling G0 states of varying duration and depth.

Racing against the clock: How flies regenerate just in time.

In this issue of Developmental Cell, Cohen et al. show that the Drosophila hindgut is a genetically tractable model for studying tissue regeneration. This tissue exhibits different regeneration strategies at different developmental times, demonstrating that the hindgut developmental clock, not tissue type, dictates the mode and capacity for regeneration.

Cell Cycle Re-entry in the Nervous System: From Polyploidy to Neurodegeneration.

Terminally differentiated cells of the nervous system have long been considered to be in a stable non-cycling state and are often considered to be permanently in G0. Exit from the cell cycle during development is often coincident with the differentiation of neurons, and is critical for neuronal function. But what happens in long lived postmitotic tissues that accumulate cell damage or suffer cell loss during aging? In other contexts, cells that are normally non-dividing or postmitotic can or re-enter the cell cycle and begin replicating their DNA to facilitate cellular growth in response to cell loss.

The Krüppel-like factor Cabut has cell cycle regulatory properties similar to E2F1.

Using a gain-of-function screen in , we identified the Krüppel-like factor Cabut (Cbt) as a positive regulator of cell cycle gene expression and cell proliferation. Enforced expression is sufficient to induce an extra cell division in the differentiating fly wing or eye, and also promotes intestinal stem cell divisions in the adult gut. Although inappropriate cell proliferation also results from forced expression of the transcription factor or its target, , Cbt does not increase E2F1 or Cyclin E activity.

Abscisic acid regulates dormancy of prostate cancer disseminated tumor cells in the bone marrow.

Prostate cancer (PCa) commonly metastasizes to the bone where the cells frequently undergo dormancy. The escape of disseminated tumor cells from cellular dormancy is a major cause of recurrence in marrow. Abscisic acid (ABA), a phytohormone, is known to regulate dormancy of plant seeds and to regulate other stress responses in plants.

Polyploidy in the adult brain.

Long-lived cells such as terminally differentiated postmitotic neurons and glia must cope with the accumulation of damage over the course of an animal's lifespan. How long-lived cells deal with ageing-related damage is poorly understood. Here we show that polyploid cells accumulate in the adult fly brain and that polyploidy protects against DNA damage-induced cell death.

Author Correction: Anticancer polymers designed for killing dormant prostate cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Changes in chromatin accessibility ensure robust cell cycle exit in terminally differentiated cells.

During terminal differentiation, most cells exit the cell cycle and enter into a prolonged or permanent G0 in which they are refractory to mitogenic signals. Entry into G0 is usually initiated through the repression of cell cycle gene expression by formation of a transcriptional repressor complex called dimerization partner (DP), retinoblastoma (RB)-like, E2F and MuvB (DREAM). However, when DREAM repressive function is compromised during terminal differentiation, additional unknown mechanisms act to stably repress cycling and ensure robust cell cycle exit.

Detection and isolation of disseminated tumor cells in bone marrow of patients with clinically localized prostate cancer.

Background: Disseminated tumor cells (DTCs) have been reported in the bone marrow (BM) of patients with localized prostate cancer (PCa). However, the existence of these cells continues to be questioned, and few methods exist for viable DTC isolation. Therefore, we sought to develop novel approaches to identify and, if detected, analyze localized PCa patient DTCs.

Anticancer polymers designed for killing dormant prostate cancer cells.

The discovery of anticancer therapeutics effective in eliminating dormant cells is a significant challenge in cancer biology. Here, we describe new synthetic polymer-based anticancer agents that mimic the mode of action of anticancer peptides. These anticancer polymers developed here are designed to capture the cationic, amphiphilic traits of anticancer peptides.

Chromatin organization changes during the establishment and maintenance of the postmitotic state.

Background: Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics.

States of G and the proliferation-quiescence decision in cells, tissues and during development.

While cellular proliferation is fundamental to the development of all multicellular organisms, the slowing or stopping of proliferation at the right places and times is equally important for proper tissue and organ development. The non-cycling state of cellular quiescence or "G" is relatively understudied compared to proliferation, given its prevalence in nature. It may seem that actively proliferating cells undergo a series of dynamic events, while quiescent cells are in a passive, static state.

Hormone-dependent control of developmental timing through regulation of chromatin accessibility.

Specification of tissue identity during development requires precise coordination of gene expression in both space and time. Spatially, master regulatory transcription factors are required to control tissue-specific gene expression programs. However, the mechanisms controlling how tissue-specific gene expression changes over time are less well understood.