Biology subjects

Cohen, E.

Publications and source records attributed to Cohen, E..

3 recordsLinked to original sources

bioRxiv2018

A Cell Cycle Switch Dictates Organ Repair and Tissue Growth Responses in The Drosophila Hindgut

Ploidy-increasing cell cycles drive tissue growth in many developing organs. Such cycles, including endocycles, are increasingly appreciated to drive tissue growth following injury or activated growth signaling in mature organs. In these organs, the regulation and distinct roles of different cell cycles remains unclear. Here, we uncover a programmed switch between cell cycles in the Drosophila hindgut pylorus. Using an acute injury model, we identify mitosis as the response in larval pyloric cells, whereas endocycles occur in adult pyloric cells. By developing a novel genetic method, DEMISE (Dual-Expression-Method-for-Induced-Site-specific-Eradication), we show the cell cycle regulator Fizzy-related dictates the decision between mitosis and endocycles. After injury, both cycles accurately restore tissue mass and genome content. However, in response to sustained growth signaling, only endocycles preserve epithelial architecture. Our data reveal distinct cell cycle programming in response to similar stimuli in mature vs. developmental states and reveal a tissue-protective role of endocycles.

cell biology↗

bioRxiv2017

A hidden Markov model approach to characterizing the photo-switching behavior of fluorophores

Fluorescing molecules (fluorophores) that stochastically switch between photon-emitting and dark states underpin some of the most celebrated advancements in super-resolution microscopy. While this stochastic behavior has been heavily exploited, full characterization of the underlying models can potentially drive forward further imaging methodologies. Under the assumption that fluorophores move between fluorescing and dark states as continuous time Markov processes, the goal is to use a sequence of images to select a model and estimate the transition rates. We use a hidden Markov model to relate the observed discrete time signal to the hidden continuous time process. With imaging involving several repeat exposures of the fluorophore, we show the observed signal depends on both the current and past states of the hidden process, producing emission probabilities that depend on the transition rate parameters to be estimated. To tackle this unusual coupling of the transition and emission probabilities, we conceive transmission (transition-emission) matrices that capture all dependencies of the model. We provide a scheme of computing these matrices and adapt the forward-backward algorithm to compute a likelihood which is readily optimized to provide rate estimates. When confronted with several model proposals, combining this procedure with the Bayesian Information Criterion provides accurate model selection.

biophysics↗

bioRxiv2017

Inter-organ regulation of Drosophila intestinal stem cell proliferation by a hybrid organ boundary zone

SUMMARY STATEMENTGene expression at the Drosophila midgut-hindgut boundary is a hybrid of both organs. Hybrid cells repress stem cell division, but boundary injury activates stem cell division through inter-organ JAK-STAT signaling.\n\nABSTRACTThe molecular identities and regulation of cells at inter-organ boundaries are often unclear, despite the increasingly appreciated role of organ boundaries in disease. Using Drosophila as a model, here we show that a specific population of adult midgut organ boundary intestinal stem cells (OB-ISCs) is regulated by the neighboring hindgut, a developmentally distinct organ. This distinct OB-ISCs control is due to proximity to a specialized transition zone between the endodermal midgut and ectodermal hindgut that shares molecular signatures of both organs, which we term the hybrid zone (HZ). During homeostasis, proximity to the HZ restrains OB-ISC proliferation. However, injury to the adult HZ/hindgut drives up-regulation of upaired-3 cytokine and OB-ISC hyperplasia. If HZ disruption is severe, hyperplastic OB-ISCs expand across the inter-organ boundary. Our data suggest that inter-organ signaling plays an important role in controlling OB-ISCs in homeostasis and injury repair, which is likely critical in prevention of disease.

developmental biology↗