Biology subjects

Kodra, A.

Publications and source records attributed to Kodra, A..

3 recordsLinked to original sources

bioRxiv2021

The TNF Egr participates in signaling during cell competition in the absence of a requirement for JNK

Numerous factors have been implicated in the cell-cell interactions that lead to elimination of cells via cell competition, a context-dependent process of cell selection in somatic tissues that is based on comparisons of cellular fitness. Here we use a series of genetic tests in Drosophila to explore the relative contribution of the pleiotropic cytokine Tumor Necrosis Factor (TNF) in Myc-mediated cell competition (also known as Myc super-competition or Myc cell competition). We find that the sole Drosophila TNF, Eiger (Egr), its receptor Grindelwald (Grnd/TNFR), and the adaptor proteins Traf4 and Traf6 are required to eliminate wild-type "loser" cells during Myc cell competition. Although typically the interaction between Egr and Grnd leads to cell death by activating the Jun N-terminal Kinase (JNK) stress signaling pathway, our experiments reveal that many components of canonical JNK signaling are dispensable for cell death in Myc cell competition, including the JNKKK Tak1, the JNKK Hemipterous (Hep) and the JNK Basket (BSK). Our results suggest that Egr/Grnd signaling participates in Myc cell competition, but functions in a role that is independent of JNK activation.

developmental biology↗

bioRxiv2021

Disruption of nuclear architecture as a cause of COVID-19 induced anosmia

Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19.

neuroscience↗

bioRxiv2020

Widely used mutants of eiger, encoding the Drosophila Tumor Necrosis factor, carry additional mutations in the NimrodC1 phagocytosis receptor

The process of apoptosis in epithelia involves activation of caspases, delamination of cells, and degradation of cellular components. Corpses and cellular debris are then rapidly cleared from the tissue by phagocytic blood cells. In studies of the Drosophila TNF, Eiger (Egr) and cell death in wing imaginal discs, the epithelial primordia of fly wings, we noticed that dying cells persisted longer in egr3 mutant wing discs than in wild type discs, raising the possibility that their phagocytic engulfment by hemocytes was impaired. Further investigation revealed that lymph glands and circulating hemocytes from egr3 mutant larvae were completely devoid of NimC1 staining, a marker of phagocytic hemocytes. Genome sequencing uncovered mutations in the NimC1 coding region that are predicted to truncate the NimC1 protein before its transmembrane domain, and provide an explanation for the lack of NimC staining. The work that we report here demonstrates the presence of these NimC1 mutations in the widely used egr3 mutant, its sister allele, egr1, and its parental strain, Regg1GS9830. As the egr3 and egr1 alleles have been used in numerous studies of immunity and cell death, it may be advisable to re-evaluate their associated phenotypes.

genetics↗