Biology subjects

Mourrain, P.

Publications and source records attributed to Mourrain, P..

5 recordsLinked to original sources

bioRxiv2026

Engulfment by brain macrophages in a short-lived vertebrate

Engulfment by macrophages is critical for waste clearance in the vertebrate brain. Understanding clearance mechanisms may open new therapeutic possibilities to counter brain aging and neurodegenerative diseases. However, few in vivo models exist to study engulfment in the brain and characterize this process during aging and across species. Here we present a genetic model for secretion of a fluorescent protein by neurons in the brain of the African turquoise killifish, the shortest-lived vertebrate that can be bred in captivity. We use this model to identify a population of brain macrophages in the killifish responsible for engulfment of material from the brain extracellular space. Intriguingly, many of these cells bear similarities to mammalian border-associated and monocyte-derived macrophages, rare subsets of macrophages in mouse and human brains noted for their engulfment capabilities. We also find that in our model, killifish brain macrophages decline in engulfment capacity with age. This work highlights how vertebrate brain macrophages, particularly those at brain border regions, can play a critical role in clearance and provides an opportunity to test interventions that can boost engulfment by these macrophages to promote brain resilience in old age and disease.

cell biology↗

bioRxiv2026

Divergence in skeletal muscle growth by differential spatial hyperplastic patterning in teleost fishes

Skeletal muscle plays important locomotive and metabolic functions, yet its formation and maintenance are processes remaining largely unclear mechanistically in any animal. Teleost fishes display extraordinary muscle growth due to their ability to undergo both hyperplasia and hypertrophy throughout life. These phenomena vary greatly even between closely related species, providing opportunities to elucidate growth dynamics and underlying mechanisms through cross-species comparisons. Using histological and genetic approaches, we compared muscle growth dynamics in three closely related danionin species with distinct growth capacities: the giant danio (Devario malabaricus), the zebrafish (Danio rerio), and Danionella cerebrum, as well as the more distantly related African turquoise killifish (Nothobranchius furzeri). Our study reveals alterations in spatial patterning of muscle hyperplasia and developmental timing to be major contributors to observed differences in muscle growth between examined species. Single-cell RNA profiling, in situ hybridization chain reaction and cell type-specific mutagenesis revealed muscle stem cell-specific expression of extracellular matrix genes that mediate stem cell activity, which in turn may drive growth differences between species. Taken together, our findings highlight autonomous regulation of muscle stem cells as a conserved but adaptable mechanism governing muscle patterning and diversification.

evolutionary biology↗

bioRxiv2023

Translational modulation by ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome

Fragile X syndrome (FXS) is caused by the functional loss of Fragile X messenger ribonucleoprotein (FMRP), a translational regulator that binds the transcripts of many proteins involved in synaptic function and plasticity. Dysregulated protein synthesis is a central effect of FMRP loss and to date direct translational modulation has not been leveraged in the treatment of FXS. Thus, we examined the effect of the small molecule translational modulator, Integrated Stress Response Inhibitor (ISRIB), in treating synaptic and behavioral symptoms of FXS. Using a combination of population-level single synapse analysis, in vivo two-photon microscopy, and behavioral analysis, we revealed a mechanism for the appearance of dense and immature dendritic spines, which are observed in human FXS patients and Fmr1 knockout (KO) mice. Our data suggest that FMRP loss at the synapse dysregulates synaptic protein abundance and that spines are disproportionately stabilized through increased PSD-95 expression but prevented from maturing through reduced synaptic accumulation of glutamate receptors. ISRIB rescues these molecular and synaptic deficits in FXS and improves social recognition in Fmr1 KO mice. These findings highlight the therapeutic potential of targeting core translational mechanisms and the differential impact of FMRP on synaptic and cellular function in FXS and neurodevelopmental disorders more broadly.

neuroscience↗

bioRxiv2020

Genome-wide molecular effects of the neuropsychiatric 16p11 CNVs in an iPSC-to-iN neuronal model

Copy number variants (CNVs), either deletions or duplications, at the 16p11.2 locus in the human genome are known to increase the risk for autism spectrum disorders (ASD), schizophrenia, and for several other developmental conditions. Here, we investigate the global effects on gene expression and DNA methylation using a 16p11.2 CNV patient-derived induced pluripotent stem cell (iPSC) to induced neuron (iN) cell model system. This approach revealed genome-wide and cell-type specific alterations to both gene expression and DNA methylation patterns and also yielded specific leads on genes potentially contributing to some of the known 16p11.2 patient phenotypes. PCSK9 is identified as a possible contributing factor to the symptoms seen in carriers of the 16p11.2 CNVs. The protocadherin (PCDH) gene family is found to have altered DNA methylation patterns in the CNV patient samples. The iPSC lines used for this study are available through a repository as a resource for research into the molecular etiology of the clinical phenotypes of 16p11.2 CNVs and into that of neuropsychiatric and neurodevelopmental disorders in general.

genetics↗

bioRxiv2018

Haplotype-phased Callithrix jacchus embryonic stem cell line for genome editing using CRISPR/Cas9

Due to anatomical and physiological similarities to humans, the common marmoset (Callithrix jacchus) is an ideal organism for the study human diseases. Researchers are currently leveraging genome-editing technologies such as CRISPR/Cas9 to genetically engineer marmosets for the in vivo biomedical modeling of human neuropsychiatric and neurodegenerative diseases. The genome characterization of these cell lines greatly reinforces these transgenic efforts. It also provides the genomic contexts required for the accurate interpretation of functional genomics data. We performed haplotype-resolved whole-genome characterization for marmoset ESC line cj367 from the Wisconsin National Primate Research Center. This is the first haplotype-resolved analysis of a marmoset genome and the first whole-genome characterization of any marmoset ESC line. We identified and phased single-nucleotide variants (SNVs) and Indels across the genome. By leveraging this haplotype information, we then compiled a list of cj367 ESC allele-specific CRISPR targeting sites. Furthermore, we demonstrated successful Cas9 Endonuclease Dead (dCas9) expression and targeted localization in cj367 as well as sustained pluripotency after dCas9 transfection by teratoma assay. Lastly, we show that these ESCs can be directly induced into functional neurons in a rapid, single-step process. Our study provides a valuable set of genomic resources for primate transgenics in this post-genome era.

genetics↗