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Fouquet, S.

Publications and source records attributed to Fouquet, S..

2 recordsLinked to original sources

Role of Neural Crest Cells in Establishing Corneal Transparency During Embryonic Development in Mice

This study deciphers the exquisitely timed cellular and molecular symphony orchestrating corneal development in mice, revealing how neural crest cells (NCCs) transition from multipotent progenitors to architects of a light-transmitting, mechanically robust stroma. Between embryonic day 10 until birth, NCCs undergo posteroanterior differentiation marked by sequential downregulation of stemness markers, paralleled by collagen I deposition initiating at E12. Stromal expansion and keratocyte-driven ECM remodelling yield precisely aligned collagen fibrils within lamellae a configuration enabling transparency through destructive interference of scattered light. Keratocytes adopt a dendritic morphology to minimize light scatter, while secreting crystallin-like proteins that match refractive indices between cells and matrix. Corneal endothelial maturation and dynamic ECM stratification culminate in a tissue optimized for both optical clarity and structural resilience. Our study elucidates the complex choreography of cellular and molecular events underpinning corneal development, offering novel insights into the acquisition of the corneas unique optical and biomechanical properties.

cell biology↗

Direct delivery of Cas9 or base editor protein and guide RNA complex enables genome editing in the retina

Genome editing by CRISPR-Cas holds promise for the treatment of retinal dystrophies. For therapeutic gene editing, transient delivery of CRISPR- Cas9 is preferable to viral delivery which leads to long-term expression with potential adverse consequences. Successful delivery of Cas9 protein and its guide RNA as ribonucleoprotein (RNP) complexes has been reported in the retinal pigment epithelium in vivo but not into photoreceptors, the main target of retinal dystrophies. Here, we investigate the feasibility of direct RNP delivery to photoreceptors and RPE cells. We show that RNPs composed of Cas9 or adenine- base editor and guide RNA, without addition of any carrier compounds, induce gene editing in retinal cells at variable rates depending on the guide RNA efficiency and on the locus. But Cas9 RNP delivery at high concentrations leads to outer retinal toxicity indicating a need to improve delivery efficiency for future therapeutic use.

bioengineering↗