Biology subjects

Sawyer, J. K.

Publications and source records attributed to Sawyer, J. K..

5 recordsLinked to original sources

bioRxiv2025

Loofah, a newly characterized adhesion protein, suppresses cell death in long-lived Drosophila hindgut enterocytes

Tissue maintenance in the presence of cell death-promoting insults requires a host of molecular mechanisms. Many studies focus on cell renewal through regeneration, while fewer studies explore mechanisms that promote cell longevity despite cell death stimuli. Here, we reveal that the adult Drosophila hindgut ileum is an excellent model to study tissue maintenance by long-lived cells. Hindgut ileal enterocytes resist the damaging detergent SDS and upstream caspase signaling by head-involution-defective (hid). This hid-induced death insensitivity arises early in adulthood and associates with numerous transcriptional changes. We interrogated 82 of these transcriptional changes in a candidate screen for enhancers of hid-induced death in the ileum. Top among our screen hits is an immunoglobulin family cell adhesion gene, CG15312. CG15312 maintains the adhesion protein FasIII on cell membranes. In hid-expressing ileal cells, CG15312 loss causes cell death and pyknotic nuclear clustering. We name this conserved gene low on-membrane fas and enhancer of hid (loofah). Our findings reveal a new mechanism linking cell adhesion and cell death resistance in a long-lived cell type. Our work establishes a new model to study tissue preservation.

cell biology↗

bioRxiv2023

Orb2 enables rare-codon-enriched mRNA expression during Drosophila neuron differentiation

Regulation of codon optimality is an increasingly appreciated layer of cell- and tissue-specific protein expression control. Here, we use codon-modified reporters to show that differentiation of Drosophila neural stem cells into neurons enables protein expression from rare-codon-enriched genes. From a candidate screen, we identify the cytoplasmic polyadenylation element binding (CPEB) protein Orb2 as a positive regulator of rare-codon-dependent expression in neurons. Using RNA sequencing, we reveal that Orb2-upregulated mRNAs in the brain with abundant Orb2 binding sites have a rare-codon bias. From these Orb2-regulated mRNAs, we demonstrate that rare-codon enrichment is important for expression control and social behavior function of the metabotropic glutamate receptor (mGluR). Our findings reveal a molecular mechanism by which neural stem cell differentiation shifts genetic code regulation to enable critical mRNA and protein expression.

developmental biology↗

bioRxiv2022

Distinct responses to rare codons in select Drosophila tissues

Codon usage bias has long been appreciated to influence protein production. Yet, relatively few studies have analyzed the impacts of codon usage on tissue-specific mRNA and protein expression. Here, we use codon-modified reporters to perform an organism-wide screen in Drosophila melanogaster for distinct tissue responses to codon usage bias. These reporters reveal a cliff-like decline of protein expression near the limit of rare codon usage in endogenously expressed Drosophila genes. Near the edge of this limit, however, we find the testis and brain are uniquely capable of expressing rare codon-enriched reporters. We define a new metric of tissue-specific codon usage, the tissue-apparent Codon Adaptation Index, to reveal a conserved enrichment for rare codon usage in the endogenously expressed genes of both Drosophila and human testis. We further demonstrate a role for rare codons in restricting protein expression of an evolutionarily young gene, RpL10Aa, to the Drosophila testis. Rare codon-mediated restriction of this testis-specific protein is critical for female fertility. Our work highlights distinct responses to rarely used codons in select tissues, revealing a critical role for codon bias in tissue biology.

developmental biology↗

bioRxiv2019

A novel intensity-specific screen identifies RpS21 as a modifier of low-intensity MAPK signaling

Signal transduction pathways are intricately fine-tuned to accomplish diverse biological processes. An example is the conserved Ras/mitogen-activated-protein-kinase (MAPK) pathway, which exhibits context-dependent signaling output dynamics and regulation. Here, by altering codon usage as a novel platform to control signaling output, we screened the Drosophila genome for modifiers specific to either weak or strong Ras-driven eye phenotypes. We mapped the underlying gene from one modifier to the ribosomal gene RpS21. RpS21 preferentially influences weak Ras/MAPK signaling outputs, and negatively regulates Ras/MAPK in multiple cell/tissue and signaling settings. In turn, MAPK signaling may regulate its own negative feedback by promoting RpS21 expression. These data show that codon usage manipulation can identify output-specific signaling regulators, and identify RpS21 as an in vivo Ras/MAPK phenotypic regulator.

genetics↗

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↗