Biology subjects

Delisle, L.

Publications and source records attributed to Delisle, L..

3 recordsLinked to original sources

bioRxiv2026

MULTIPLE DEFECTS IN MOUSE STEM CELL BASED EMBRYO MODELS LACKING ALL HOX FUNCTION

Mammals have four genomic copies of an ancestral Hox cluster, with a total of 39 genes. While gene inactivation approaches and full cluster deletions have revealed their critical functions during early development, the effect of removing all Hox function has remained elusive due to both biological and technological challenges. We have used mouse gastruloids, an ES cells-derived embryo model where Hox genes are properly activated in time and space, to assess the effect of their complete absence. We report that gastruloids lacking Hox function can still elongate and reach a general shape resembling their control counterparts, with a well-established AP polarity. However, unlike controls, they fail to produce any endoderm and are unable to properly segment their presomitic mesoderm into persistent somite-like structures. Instead, they produce a type of mesoderm with a more anterior identity. We thus propose that, in this system at least, HOX proteins are necessary to posteriorize an existing anterior ground-state structure, in part by promoting and/or maintaining the epithelialization of cellular condensations. Multiomes analysis revealed range of modifications in chromatin accessibility in the absence of any HOX proteins, involving in particular variations in the binding of the co-factor PBX1. In contrast, neuro-mesodermal progenitor (NMP) cells are not overtly affected in mutant gastruloids, even though they normally initiate strong Hox gene transcription, suggesting that these cells are used as vehicles to translate a temporal sequence of activation into an AP colinear transcript distribution, which becomes functional at a later stage only.

Developmental Biology↗

bioRxiv2025

A novel crustavirus associated with tail fan necrosis in New Zealand red rock lobsters, Jasus edwardsii

Tail fan necrosis (TFN) is a shell disease affecting spiny lobsters outer integument, with significant implications for the health and commercial viability of red rock lobsters (Jasus edwardsii) in New Zealand. Despite its impact, the potential role of a microbial agent in TFN remains poorly understood. Here, we conducted metatranscriptomic analyses on matching uropod and haemolymph samples from 15 red rock lobsters exhibiting TFN symptoms to characterise the associated microbial communities and search for putative candidates for further investigation. We report the discovery of a novel crustavirus (family: Nyamiviridae), named Red rock lobster crustavirus (RRLCV), consistently present in the uropod tissues of all sampled lobsters with TFN. RRLCVs presence and high abundance in uropod tissues suggest a potential association with TFN, although we found no direct relationship between viral abundance and TFN severity metrics, such as tissue loss. We also identified 30 bacterial genera across uropod samples, including previously associated groups, however, these were detected inconsistently. Our findings raise new questions about the tissue tropism, transmission, and potential pathogenicity of RRLCV in red rock lobsters. While TFN appears to be a multifactorial condition, RRLCV represents a promising candidate for further research into its role in the development of this disease.

microbiology↗

bioRxiv2017

LARGE-SCALE GENOMIC REORGANIZATIONS OF TOPOLOGICAL DOMAINS (TADs) AT THE HoxD LOCUS

BackgroundThe transcriptional activation of Hoxd genes during mammalian limb development involves dynamic interactions with the two Topologically Associating Domains (TADs) flanking the HoxD cluster. In particular, the activation of the most posterior Hoxd genes in developing digits is controlled by regulatory elements located in the centromeric TAD (C-DOM) through long-range contacts. To assess the structure-function relationships underlying such interactions, we measured compaction levels and TAD discreteness using a combination of chromosome conformation capture (4C-seq) and DNA FISH.\n\nResultsWe challenged the robustness of the TAD architecture by using a series of genomic deletions and inversions that impact the integrity of this chromatin domain and that remodel the long-range contacts. We report multi-partite associations between Hoxd genes and up to three enhancers and show that breaking the native chromatin topology leads to the remodelling of TAD structure.\n\nConclusionsOur results reveal that the re-composition of TADs architectures after severe genomic re-arrangements depends on a boundary-selection mechanism that uses CTCF-mediated gating of long-range contacts in combination with genomic distance and, to a certain extent, sequence specificity.

genomics↗