Biology subjects

de Boissier, P.

Publications and source records attributed to de Boissier, P..

3 recordsLinked to original sources

bioRxiv2026

MYCN-induced lineage infidelity initiates SHH medulloblastoma-like tumors outside the canonical lineage of origin

Amplification and high expression of MYCN and MYC are recurrent features of medulloblastoma and other pediatric cancers, yet how these proto-oncogenes interact with developmental programs to initiate tumorigenesis remains unclear. Here, we combine the experimental accessibility of the avian embryo with single-cell transcriptomics to investigate how MYCN overexpression reshapes cerebellar lineage trajectories. While MYCN broadly promotes transient overproliferation, enhanced biosynthesis and delayed neural maturation, we find that these effects are insufficient to drive tumorigenesis. Instead, tumorigenic competence is restricted to a discrete population of ATOH1+ isthmic progenitors, which reproducibly expands into extracerebellar tumors that transcriptionally resemble SHH medulloblastoma, partially recapitulating the granule cell lineage hierarchy. By reconstructing the earliest stages of tumor initiation, we show that MYCN first expands these progenitors and then redirects them toward a hybrid PAX6 granule cell progenitor-like state. Blocking PAX6 transcriptional activity abolishes tumorigenesis of the reprogrammed population, demonstrating that cooption of this lineage program is functionally required for tumor growth. Our findings reveal that MYCN-induced oncogenicity in the cerebellum proceeds through a three-step temporal sequence driven by the erosion of lineage restrictions.

cancer biology↗

bioRxiv2022

The evo-MOTiF pipeline and database for studying protein motif evolution in a structural context

Short linear motifs (SLiMs) in proteins are short functionally independent sequence stretches with a defined function and required for proteins to interact with their environment. Their functional importance makes it interesting to analyse SLiM features further, such as their structural or evolutionary properties, to understand better how SLiMs evolve to shape protein functions. We developed an automated pipeline to analyse features of SLiMs, called evo-MOTiF. This pipeline takes as input a single protein sequence and its associated SLiM(s) and returns a set of scores associated with SLiM features, including their disorder, as well as their overall, positional and amino acid property conservation. To store and easily mine data from the evo-MOTiF pipeline, we developed the evo-MOTiF database, which currently holds [~]9500 motifs, combining data from ELM, PhosphoSitePlus, as well as from cross-linking mass-spectrometry (XL-MS) experiments. The evo-MOTiF database distinguishes itself further by allowing effortless filtering for SLiMs with specific properties, such as disorder, or conservation in evolution and by providing evolutionary, as well as structural information for SLiMs. Preliminary analysis of SLiM features reveals weak negative correlation between disorder and overall, positional, as well as amino acid property conservation, which is in support of previous observations on smaller datasets. The evo-MOTiF pipeline and database are freely available at https://gitlab.com/habermann_lab/slims and http://etnadb.ibdm.univ-mrs.fr/index.php, respectively.

bioinformatics↗

bioRxiv2021

A Tad-like apparatus is required for contact-dependent prey killing in predatory social bacteria

Myxococcus xanthus, a soil bacterium, predates collectively using motility to invade prey colonies. Prey lysis is mostly thought to rely on secreted factors, cocktails of antibiotics and enzymes, and direct contac with Myxococcus cells. In this study, we show that on surfaces the coupling of A-motility and contact-dependent killing is the central predatory mechanism driving effective prey colony invasion and consumption. At the molecular level, contact-dependent killing involves a newly discovered type IV filament-like machinery (Kil) that both promotes motility arrest and prey cell plasmolysis. In this process, Kil proteins assemble at the predator-prey contact site, suggesting that they allow tight contact with prey cells for their intoxication. Kil-like systems form a new class of Tad-like machineries in predatory bacteria, suggesting a conserved function in predator-prey interactions. This study further reveals a novel cell-cell interaction function for bacterial pili-like assemblages.

microbiology↗