Biology subjects

MARTIN, F.

Publications and source records attributed to MARTIN, F..

3 recordsLinked to original sources

bioRxiv2025

Lineage of origin-specific developmental programs drive the behaviors of malignant cells in an avian embryo model of human Medulloblastoma subgroups

Tumoral cells of medulloblastoma (MB) subgroups (SHH, G3 and G4) display a close transcriptomic proximity to early neuronal progenitors that migrate to form the embryonic cerebellum. With the aim of exploring functional proximities between MB cells and their physiological counterparts, we established a model of transplantation of human MB cells into the cerebellum of chick embryos in vivo and ex ovo. Light-sheet imaging of embryos grafted with cell lines and patient biopsies of MB SHH, G3 and G4 revealed the formation of primary tumors within a few days, whose topography matched that of the different MB subgroups on patients MRI. We found that transplanted MB cells adopted morphological and migratory features specific of their respective lineage of origin. Combining transcriptomic and functional approaches, we found that MB G3 tumoral cells exploit the canonical SLIT migration developmental signaling at disease emergence. This signaling is maintained in MB G3 patients and is associated with tumor aggressivity and poor prognosis.

cancer biology↗

bioRxiv2025

N-terminally acetylated Met11-Tau: a new pathological truncated Tau species with functional relevance in Alzheimer Disease

Neurodegenerative diseases like Alzheimers disease (AD) are characterized by progressive accumulation of pathological Tau proteins. Among the diverse Tau species, truncated variants are emerging as key contributors, yet their identity remains elusive, particularly for the N-terminal truncated ones. The present study identifies and characterizes a novel N-terminally truncated and N-alpha-acetylated form of the Tau protein. Using a newly developed antibody specifically targeting this truncated variant, we demonstrate that this species accumulates early in degenerating neurons in both transgenic mouse models of AD-related Tau pathology and post-mortem brain tissues from AD patients. Importantly, in vivo functional experiments reveal that expression of this truncated Tau species exacerbates Tau pathology, whereas targeted immunotherapeutic with the specific antibody significantly reduces pathological Tau accumulation and prevents associated memory impairments. These findings position this newly identified Tau variant as both a marker of neurofibrillary degeneration and a pathogenic driver of neurodegeneration and supports its potential as a therapeutic target in Tau-related disorders, notably AD.

neuroscience↗

bioRxiv2024

Critical cis-parameters influence STructure Assisted RNA Translation (START) initiation on non-AUG codons in eukaryotes

In eukaryotes, translation initiation is a highly regulated process, which combines cis- regulatory sequences located on the messenger RNA along with trans-acting factors like eukaryotic initiation factors (eIF). One critical step of translation initiation is the start codon recognition by the scanning 43S particle, which leads to ribosome assembly and protein synthesis. In this study, we investigated the involvement of secondary structures downstream the initiation codon in the so-called START (Structure-Assisted RNA translation) mechanism on AUG and non-AUG translation initiation. The results demonstrate that downstream secondary structures can efficiently promote non-AUG translation initiation provided that they are stable enough to stall a scanning 43S particle and that they are located at an optimal distance from this non-AUG codon to trigger and stabilize the codon-anticodon base-pairing in the P site. The required stability of the downstream structure for efficient translation initiation varies in distinct cell types. We extended this study to genome-wide analysis of the Homo sapiens alternative translation initiation sites and discovered 556 of them starting with an AUG and 506 starting with a non-AUG that contained a downstream RNA structure at an optimal distance and with a predicted stability of at least -15 kcal/mol. We validated the impact of these structures on translation initiation for several selected uORFs.

molecular biology↗