Wells, M. B. | bioRxiv Science

bioRxiv2021

The Ribb-osome: Ribbon boosts ribosomal protein gene expression to coordinate organ form and function

Cell growth is well defined for the late (post-embryonic) stages of development, but evidence for early (embryonic) cell growth during post-mitotic morphogenesis is quite limited. Here, we identify early cell growth as a key characteristic of tubulogenesis in the Drosophila embryonic salivary gland (SG). A BTB/POZ domain nuclear factor, Ribbon (Rib), mediates this early cell growth. Rib binds the transcription start site of nearly every SG-expressed ribosomal protein gene (RPG) and is required for full expression of all RPGs tested. Rib binding to RPG promoters in vitro is weak and not sequence-specific, suggesting that specificity is achieved through co-factor interactions. Consistent with this hypothesis, we demonstrate Ribs ability to physically interact with each of the three known contributors to RPG transcription. Surprisingly, Rib-dependent early cell growth in another tubular organ--the embryonic trachea--is not mediated by direct RPG transcription. These findings support a model of early cell growth sustained by transcriptional regulatory networks customized for organ form and function.

developmental biology↗

bioRxiv2018

Regulation of midgut cell proliferation impacts Aedes aegypti susceptibility to dengue virus

Aedes aegypti is the vector of some of the most important vector-borne diseases like Dengue, Chikungunya, Zika and Yellow fever, affecting millions of people worldwide. The cellular processes that follow a blood meal in the mosquito midgut are directly associated with pathogen transmission. We studied the homeostatic response of the midgut against oxidative stress, as well as bacterial and dengue virus (DENV) infections, focusing on the proliferative ability of the intestinal stem cells (ISC). Inhibition of the peritrophic matrix (PM) formation led to an increase in ROS production by the epithelial cells in response to contact with the resident microbiota, suggesting that maintenance of low levels of ROS in the intestinal lumen is key to keep ISCs division in balance. We show that dengue virus infection induces midgut cell division in both DENV susceptible (Rockefeller) and refractory (Orlando) mosquito strains. However, the susceptible strain delays the activation of the regeneration process compared with the refractory strain. Impairment of the Delta/Notch signaling, by silencing the Notch ligand Delta using RNAi, significantly increased the susceptibility of the refractory strains to DENV infection of the midgut. We propose that this cell replenishment is essential to control viral infection in the mosquito. Our study demonstrates that the intestinal epithelium of the blood fed mosquito is able to respond and defend against different challenges, including virus infection. In addition, we provide unprecedented evidence that the activation of a cellular regenerative program in the midgut is important for the determination of the mosquito vectorial competence.

cell biology↗