Biology subjects

Speder, P.

Publications and source records attributed to Speder, P..

4 recordsLinked to original sources

bioRxiv2025

Cell competition overcomes host tissue resistance to unleash tumour growth in a Drosophila brain cancer model

Primary tumours of the central nervous system are extremely aggressive and often incurable. While tumours are known to interact with their microenvironment, how the interplay between tumour cells and the host tissue controls tumour progression remains elusive. We addressed this question in a Drosophila model of cancer stem cell-driven tumour which originates during development and grows extensively within a network of cortex glia cells (CG) through adulthood. We found that tumour growth induces progressive remodeling of the CG network and leads to CG apoptosis through cancer stem cell-driven competition, a process which in turn unleashes tumour growth. Notably, preventing CG death reduces tumour growth, revealing a resistance capacity within the CG. Transcriptional profiling of CG cells at different stages revealed a biphasic response, featuring an early specific signature followed by a later collapse of essential cellular functions and pathways, including the conserved JNK pathway. JNK signalling in CG normally plays a neuroprotective role and initially hinders tumour progression, providing resistance. However, its subsequent downregulation eventually brings the collapse of the host tissue, ultimately curbing tumour growth. This study uncovers a dynamic and complex interplay between host tissue resistance and tumour-driven competition, which shapes tumour progression.

cell biology↗

bioRxiv2024

Adhesion-Controlled Mechanics of the Glial Niche Regulate Neural Stem Cell Proliferative Potential

Controlled proliferation of neural stem cells (NSCs) builds a functional nervous system during development. While their cellular niche is recognized as a signalling hub, the contribution of its structure and mechanics in regulating neurogenesis remains unexplored. The Drosophila larval central nervous system contains self-renewing NSCs in close contact with cortex glial cells. Transcriptomics identified a triad of immunoglobulin superfamily cell adhesion molecules (Dpr10/Dpr6 in glia and DIP- in NSCs) which physically and mechanically connect the NSC and glial membranes, acting as mechanoregulators. Their disruption increases glial cortical tension, causing non-autonomous mitotic defects in NSCs, characterized by abnormal spindle morphologies and impaired mitotic progression. Additionally, elevated glial tensile forces increase Lamin content in NSCs, a protective response also resulting in nuclear deformation. Ultimately NSC proliferative potential and genome integrity are compromised. Our study reveals that the native mechanical properties of the niche are transmitted to NSCs and regulate their function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=156 SRC="FIGDIR/small/628019v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@18137f8org.highwire.dtl.DTLVardef@819740org.highwire.dtl.DTLVardef@1f0ed0forg.highwire.dtl.DTLVardef@5ba0e4_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

A corset of adhesions during development establishes individual neural stem cell niches and controls adult behaviour

Neural stem cells (NSCs) reside in a defined cellular microenvironment, the niche, which supports the generation and integration of neuronal lineages. The mechanisms building a sophisticated niche structure around NSCs, and their functional relevance for neurogenesis are yet to be understood. In the Drosophila larval brain, the cortex glia (CG) encase individual NSC lineages, organizing the stem cell population and newborn neurons into a stereotypic structure. We first found that lineage information is dominant over stem cell fate. We then discovered that, in addition to timing, the balance between multiple adhesion complexes supports the individual encasing of NSC lineages. An intra-lineage adhesion through homophilic Neuroglian interactions provides strong binding between cells of a same lineage, while a weaker interaction through Neurexin-IV exists between CG to NSC lineages. Their loss leads to random, aberrant grouping of several NSC lineages together, and to altered axonal projection of newborn neurons. Further, we link the loss of these two adhesion complexes during development to locomotor hyperactivity in the resulting adults. Altogether, our findings identify a corset of adhesions building a neurogenic niche at the scale of individual stem cell and provide the proof-of-principle that mechanisms supporting niche formation during development define adult behaviour.

developmental biology↗

bioRxiv2020

An original model of brain infection identifies B Streptococcus lipoprotein Blr as a ligand exploiting host endocytosis for blood-brain barrier crossing.

Pathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We identified several mammalian pathogens able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucin-rich Blr, were important for BBB crossing and virulence in Drosophila. Further, we identified (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we demonstrated that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results support the relevance of Drosophila for studying host-pathogen interactions and identify a new mechanism by which pathogens exploit host barriers to generate brain infection.

microbiology↗