Biology subjects

Richards, Z.

Publications and source records attributed to Richards, Z..

3 recordsLinked to original sources

bioRxiv2025

A hormonally regulated gating mechanism controls EMT timing to ensure progenitor cell specification occurs prior to epithelial breakdown

Epithelial-to-mesenchymal transitions (EMTs) are essential for morphogenesis, converting static epithelial cells into migratory mesenchymal cells. As EMT disrupts epithelial barriers, its timing must be tightly regulated during development. We investigated this regulation in the Drosophila posterior embryonic midgut, where the GATA transcription factor Serpent (Srp) drives a collective partial EMT in the principal midgut epithelial cells (PMECs). Srp is expressed well before PMEC-EMT initiation and is also required for an earlier event: the specification and delamination of endoblasts, which give rise to different midgut lineages including adult midgut progenitors (AMPs). Here we identify the steroid hormone ecdysone as a temporal cue that triggers PMEC-EMT. Although Srp activates and represses numerous genes during early stages of midgut development, including polarity regulators such as crumbs (crb), the removal of polarity proteins and E-Cadherin from the membrane of PMECs only properly occurs in the presence of ecdysone signalling. This suggests that Srp primes cells transcriptionally for EMT, which proceeds only once polarity and adhesion proteins are downregulated post-translationally. When PMECs undergo a premature EMT, this leads to a reduction in the number of progenitor cells, suggesting that maintaining epithelial integrity until after endoblasts are selected is crucial for early fate decisions. These findings reveal that ecdysone functions as a EMT gatekeeper, ensuring that EMT is temporally restricted to occur only after progenitor specification, and in coordination with other developmental processes. More broadly, our work shows that in this context, transcriptional priming of EMT can be uncoupled from its execution, which is post-translationally triggered by hormonal signals. Given the conserved role of nuclear steroid hormone receptors as GATA co-factors and their association with poor prognosis in cancer, this may represent a broader strategy by which systemic cues regulate EMT in development and cancer.

developmental biology↗

bioRxiv2022

Viral burdens are associated with age and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection related sampling bias.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burdens, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. Analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior infection, the average Ct value was 0.94 lower among Alpha variant infections, compared those with the predecessor strain, B.1.177. However, among vaccinated individuals, it was 0.34 lower among Delta variant infections, compared to those with the Alpha variant. In addition, the average Ct value decreased by 0.20 for every 10 year age increment of the infected individual. In summary, within-host viral burdens are associated with age, in addition to the interplay of vaccination status and viral variant.

genetics↗

bioRxiv2021

Selecting species for restoration in foundational assemblages

O_LIHumans have long sought to restore species, but little attention has been directed at how to best select a subset of foundation species for maintaining rich assemblages that support ecosystems, like coral reefs and rainforests that are increasingly threatened by environmental change. C_LIO_LIWe propose a two-part hedging approach that selects optimized sets of species for restoration. The first part acknowledges that biodiversity supports ecosystem functions and services, and so it takes precaution against loss by ensuring an even spread of phenotypic traits. The second part maximizes species and ecosystem persistence by weighting species based on characteristics that are known to improve ecological persistence--e.g., abundance, species range and tolerance to environmental change. C_LIO_LIUsing existing phenotypic trait and ecological characteristic data for reef building corals, we identified sets of ecologically persistent species by examining marginal returns in occupancy of phenotypic trait space. We compared optimal sets of species with those from the worlds southern-most coral reef which naturally harbors low coral diversity to show these occupy much of the trait space. Comparison with an existing coral restoration program indicated that current corals used for restoration only cover part of the desired trait space and may be improved by including species with different traits. C_LIO_LISynthesis and applications. While there are many possible criteria for selecting species for restoration, the approach proposed here addresses the need to insure against unpredictable losses of ecosystem services by focusing on a wide range of phenotypic traits and ecological characteristics. Furthermore, the flexibility of the approach enables the functional goals of restoration to vary depending on environmental context, stakeholder values, and the spatial and temporal scales at which meaningful impacts can be achieved. C_LI

ecology↗