Biology subjects

Derderian, C.

Publications and source records attributed to Derderian, C..

3 recordsLinked to original sources

bioRxiv2025

microRNA-Mediated Effects of Caloric Restriction on Trophoblast Invasion and Angiogenic Signaling in a Mouse Model of Fetal Growth Restriction

Trophoblast invasion is essential for normal placentation, with failure resulting in a fetal growth restriction (FGR) phenotype. Utilizing a calorie-restricted mouse model, we report progressive epigenetic, molecular, and phenotypic placental changes throughout gestation. Following maternal caloric restriction initiated at E9, we observed a significant reduction in fetal and placental weights beginning at E12.5, with persistent growth restriction at E14.5, E16.5, and E17.5. Immunohistochemistry of the decidual invasion site at E17.5 demonstrated reduced 1) decidual depth, 2) trophoblast invasion distance, and 3) trophoblast quantity within the decidua. Preceding these phenotypic changes, RT-qPCR revealed downregulation of trophoblast invasion and angiogenesis genes, including MMP2, MMP9, EFNA1, Rac1, Rras, ASCL2, TRAP2C, Prl7b1, VEGFa, VEGFb, PDGF, and AKT3, beginning as early as E14.5. Notably, microRNA sequencing at E12.5, prior to these transcriptional changes, identified significant upregulation of miR-503-5p, a predicted inhibitor of several of these pathways. The summation of these observations suggests miR-503-5p may be an early driver of placental dysfunction in FGR, linking maternal malnutrition to impaired trophoblast invasion and angiogenesis. These findings provide insight into the molecular mechanisms underlying placental insufficiency and highlight miR-503-5p as a potential therapeutic target for improving pregnancy outcomes in FGR.

molecular biology↗

bioRxiv2024

The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture

Cilia are essential organelles and variants in genes governing ciliary function result in ciliopathic diseases. The Ciliogenesis and PLANar polarity Effectors (CPLANE) protein complex is essential for ciliogenesis in animals models but remains poorly defined. Notably, all but one subunit of the CPLANE complex have been implicated in human ciliopathy. Here, we identify three families in which variants in the remaining CPLANE subunit CPLANE2/RSG1 also cause ciliopathy. These patients display cleft palate, tongue lobulations and polydactyly, phenotypes characteristic of Oral-Facial-Digital Syndrome. We further show that these alleles disrupt two vital steps of ciliogenesis, basal body docking and recruitment of intraflagellar transport proteins. Moreover, APMS reveals that Rsg1 binds the CPLANE and also the transition zone protein Fam92 in a GTP-dependent manner. Finally, we show that CPLANE is generally required for normal transition zone architecture. Our work demonstrates that CPLANE2/RSG1 is a causative gene for human ciliopathy and also sheds new light on the mechanisms of ciliary transition zone assembly.

cell biology↗

bioRxiv2021

Isolation and in vitro culture of primary pia mater cells

The meninges remain an unexplored area of neurobiology. These structures play host to dozens of morbid pathologies. This protocol provides a reliable way to identify and isolate pial cells from mice using robust markers of pial identity in mouse and human tissues. We describe a protocol for the extraction of pia mater cells from mice and their culture as primary cells in vitro. Using an array of transcriptomic, histological, and flow cytometric analyses, we identified Icam1 and Slc38a2 as two novel pia mater markers in vitro and in vivo. Our results confirm the fibroblastoid nature of pial cells and their ability to form a sheet-like layer that covers the brain parenchyma. To our knowledge, this is the first published protocol for the isolation, tissue culture, and marker identification of pial cells from mice. These findings will enable researchers in CNS barriers to describe pial cell functions in both health and disease.

neuroscience↗