Biology subjects

Saadaoui, M.

Publications and source records attributed to Saadaoui, M..

5 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↗

bioRxiv2024

Inferring the location and orientation of cell divisions on time-lapse image sequences

We propose a two-stage supervised framework for characterizing cell divisions in 2D and 3D time-lapse microscopy. First, we recast division detection as a semantic segmentation task on image sequences. Second, a local regression model estimates the orientation and distance between daughter cells for each event. We validate this framework using image sequences of avian neuroepithelium and mouse gastruloids. Our results demonstrate that high performance is achieved with efficient architectures, namely a U-Net for segmentation and a CNN for regression, that are optimized through systematic hyperparameter exploration. We find that integrating temporal context via multiple consecutive frames significantly boosts segmentation accuracy. We achieve F1 scores exceeding 94% (2D+t) and 90% (3D+t), with orientation accuracy approaching the uncertainty limit of manual annotation. We provide the full codebase and training workflow, specifically designed for datasets where traditional tracking is challenging.

biophysics↗

bioRxiv2023

Evolutionarily conserved role of serotonin signaling in regulating actomyosin contractility during morphogenesis

Serotonin is a neurotransmitter that signals through 5-HT receptors to control key functions in the nervous system. Serotonin receptors are also ubiquitously expressed in various organs and have been detected in embryos of different organisms. Potential morphogenetic functions of serotonin signaling have been proposed based on pharmacological studies but a mechanistic understanding is still lacking. Here, we uncover a role of serotonin signaling in axis extension of Drosophila embryos by regulating MyosinII (MyoII) activation, cell contractility and cell intercalation. We find that serotonin and serotonin receptors 5HT2A and 5HT2B form a signaling module that quantitatively regulates the amplitude of planar polarized MyoII contractility specified by Toll receptors and the GPCR Cirl. Remarkably, serotonin signaling also regulates actomyosin contractility at cell junctions, cellular flows and epiblast morphogenesis during chicken gastrulation. This phylogenetically conserved mechanical function of serotonin signaling in regulating actomyosin contractility and tissue flow reveals an ancestral role in morphogenesis of multicellular organisms.

developmental biology↗

bioRxiv2019

Elevation of FAM129A in neutrophils exposed to serum of patients with severe sepsis: in silico investigations during a hands on training workshop and follow on validation of protein expression in neutrophils

Steps involved in reductionist investigation approaches can be imitated using public transcriptome datasets as source of training material. In the present report trainees explored an apparent gap in biological knowledge for FAM129A (family with sequence similarity 129 member A). Elevated abundance of FAM129A transcripts were observed in a transcriptome dataset where neutrophils were exposed in vitro to plasma of patients with sepsis. However, no literature linking FAM129A and either neutrophils, sepsis or inflammation could be identified. Additional datasets were selected to independently validate this initial observation and further explore differential expression of FAM129A in the context of sepsis studies. Follow on investigations carried out at the bench confirmed restriction of the expression of FAM129A protein at the surface of circulating blood neutrophils and monocytes. A potential role for FAM129A in neutrophil survival was inferred from profiling of literature associated with FAM129A, which remains to be investigated in further follow on investigations.

immunology↗

bioRxiv2018

A tensile ring drives tissue flows to shape the gastrulating amniote embryo

Tissue morphogenesis is driven by local cellular deformations, themselves powered by contractile actomyosin networks. While it is well demonstrated that cell-generated forces at the microscopic scale underlie a variety of local morphogenetic processes (e.g. lengthening/ narrowing1-4, bending5-8, or folding9,10), how such local forces are transmitted across tissues to shape them at a mesoscopic scale remains largely unknown. Here, by performing a quantitative analysis of gastrulation in entire avian embryos, we show that the formation of the primitive streak and the associated large-scale rotational tissue flows (i.e. polonaise movements11,12) are integral parts of a global process that is captured by the laws of fluid mechanics. We identify a large-scale supracellular actomyosin ring (2 mm in diameter and 250 m thick) that shapes the embryo by exerting a graded tension along the margin between the embryonic and extra-embryonic territories. Tissue-wide flows arise from the transmission of these localized forces across the embryonic disk and are quantitatively recapitulated by a fluid-mechanical model based on the Stokes equations for viscous flow. We further show that cell division, the main driver of cell rearrangements at this stage13, is required for fluid-like behavior and for the progress of gastrulation movements. Our results demonstrate the power of a hydrodynamic approach to tissue-wide morphogenetic processes14-16 and provide a simple, unified mechanical picture of amniote gastrulation. A tensile embryo margin, in addition to directing tissue motion, could act as an interface between mechanical and molecular cues, and play a central role in embryonic self-organization.

developmental biology↗